Association of vitamin D receptor gene polymorphisms with type 2 diabetes mellitus in Taif population: a case-control study / Associação de polimorfismos do gene do receptor de vitamina D com diabetes mellitus tipo 2 na população Taif: um estudo de caso-controle

Abstract Several reasons may underlie the dramatic increase in type2 diabetes mellitus. One of these reasons is the genetic basis and variations. Vitamin D receptor polymorphisms are associated with different diseases such as rheumatoid arthritis and diabetes. The aim of this study is to investigate the possible association of two identified mutations ApaI (rs7975232) and TaqI (rs731236). Eighty-nine healthy individuals and Fifty-six Type 2 Diabetic (T2D) patients were investigated using RFLP technique for genotyping and haplotyping as well. The distribution of Apal genotypes was not statistically significant among the control (P=0.65) as well as for diabetic patients (P=0.58). For Taql allele frequencies of T allele was 0.61 where of G allele was 0.39. The frequency distribution of Taql genotypes was not statistically significant among the control (P=0.26) as well as diabetic patients (P=0.17). Relative risk of the allele T of Apa1 gene is 1.28 and the odds ratio of the same allele is 1.53, while both estimates were < 1.0 of the allele G. Similarly, with the Taq1 gene the relative risk and the odds ratio values for the allele T are 1.09 and 1.27 respectively and both estimates of the allele C were 0.86 for the relative risk and 0.79 for the odds ratio. The pairwise linkage disequilibrium between the two SNPs Taq1/apa1 was statistically significant in control group (D = 0.218, D' = 0.925 and P value < 0.001) and similar data in diabetic groups (D = 0.2, D' = 0.875 and P value < 0.001). These data suggest that the T allele of both genes Apa1 and Taq1 is associated with the increased risk of type 2 diabetes. We think that we need a larger number of volunteers to reach a more accurate conclusion.

Resumo Várias razões podem estar subjacentes ao aumento dramático da diabetes mellitus tipo 2. Um desses motivos é a base genética e variações. Os polimorfismos do receptor da vitamina D estão associados a diferentes doenças, como artrite reumatoide e diabetes. O objetivo deste estudo é investigar a possível associação de duas mutações identificadas ApaI (rs7975232) e TaqI (rs731236). Oitenta e nove indivíduos saudáveis ​​e 56 pacientes com diabetes tipo 2 (T2D) foram investigados usando a técnica RFLP para genotipagem e haplotipagem também. A distribuição dos genótipos Apal não foi estatisticamente significativa entre o controle (P = 0,65), bem como para os pacientes diabéticos (P = 0,58). Para as frequências do alelo Taql, o alelo T foi de 0,61, onde o alelo G foi de 0,39. A distribuição de frequência dos genótipos Taql não foi estatisticamente significativa entre o controle (P = 0,26), bem como os pacientes diabéticos (P = 0,17). O risco relativo do alelo T do gene Apa1 é 1,28 e a razão de chances do mesmo alelo é 1,53, enquanto ambas as estimativas foram < 1,0 do alelo G. Da mesma forma, com o gene Taq1, os valores de risco relativo e razão de chances para o alelo T são 1,09 e 1,27, respectivamente, e ambas as estimativas do alelo C foram de 0,86 para o risco relativo e 0,79 para o odds ratio. O desequilíbrio de ligação par a par entre os dois SNPs Taq1 / apa1 foi estatisticamente significativo no grupo de controle (D = 0,218, D' = 0,925 e valor P < 0,001) e dados semelhantes em grupos diabéticos (D = 0,2, D' = 0,875 e valor P < 0,001). Esses dados sugerem que o alelo T de ambos os genes Apa1 e Taq1 está associado ao aumento do risco de diabetes tipo 2. Achamos que precisamos de um número maior de voluntários para chegar a uma conclusão mais precisa.

Association of vitamin D receptor gene polymorphisms with type 2 diabetes mellitus in Taif population: a case-control study

Abstract Several reasons may underlie the dramatic increase in type2 diabetes mellitus. One of these reasons is the genetic basis and variations. Vitamin D receptor polymorphisms are associated with different diseases such as rheumatoid arthritis and diabetes. The aim of this study is to investigate the possible association of two identified mutations ApaI (rs7975232) and TaqI (rs731236). Eighty-nine healthy individuals and Fifty-six Type 2 Diabetic (T2D) patients were investigated using RFLP technique for genotyping and haplotyping as well. The distribution of Apal genotypes was not statistically significant among the control (P=0.65) as well as for diabetic patients (P=0.58). For Taql allele frequencies of T allele was 0.61 where of G allele was 0.39. The frequency distribution of Taql genotypes was not statistically significant among the control (P=0.26) as well as diabetic patients (P=0.17). Relative risk of the allele T of Apa1 gene is 1.28 and the odds ratio of the same allele is 1.53, while both estimates were 1.0 of the allele G. Similarly, with the Taq1 gene the relative risk and the odds ratio values for the allele T are 1.09 and 1.27 respectively and both estimates of the allele C were 0.86 for the relative risk and 0.79 for the odds ratio. The pairwise linkage disequilibrium between the two SNPs Taq1/apa1 was statistically significant in control group (D = 0.218, D' = 0.925 and P value 0.001) and similar data in diabetic groups (D = 0.2, D' = 0.875 and P value 0.001). These data suggest that the T allele of both genes Apa1 and Taq1 is associated with the increased risk of type 2 diabetes. We think that we need a larger number of volunteers to reach a more accurate conclusion.

Resumo Várias razões podem estar subjacentes ao aumento dramático da diabetes mellitus tipo 2. Um desses motivos é a base genética e variações. Os polimorfismos do receptor da vitamina D estão associados a diferentes doenças, como artrite reumatoide e diabetes. O objetivo deste estudo é investigar a possível associação de duas mutações identificadas ApaI (rs7975232) e TaqI (rs731236). Oitenta e nove indivíduos saudáveis e 56 pacientes com diabetes tipo 2 (T2D) foram investigados usando a técnica RFLP para genotipagem e haplotipagem também. A distribuição dos genótipos Apal não foi estatisticamente significativa entre o controle (P = 0,65), bem como para os pacientes diabéticos (P = 0,58). Para as frequências do alelo Taql, o alelo T foi de 0,61, onde o alelo G foi de 0,39. A distribuição de frequência dos genótipos Taql não foi estatisticamente significativa entre o controle (P = 0,26), bem como os pacientes diabéticos (P = 0,17). O risco relativo do alelo T do gene Apa1 é 1,28 e a razão de chances do mesmo alelo é 1,53, enquanto ambas as estimativas foram 1,0 do alelo G. Da mesma forma, com o gene Taq1, os valores de risco relativo e razão de chances para o alelo T são 1,09 e 1,27, respectivamente, e ambas as estimativas do alelo C foram de 0,86 para o risco relativo e 0,79 para o odds ratio. O desequilíbrio de ligação par a par entre os dois SNPs Taq1 / apa1 foi estatisticamente significativo no grupo de controle (D = 0,218, D' = 0,925 e valor P 0,001) e dados semelhantes em grupos diabéticos (D = 0,2, D' = 0,875 e valor P 0,001). Esses dados sugerem que o alelo T de ambos os genes Apa1 e Taq1 está associado ao aumento do risco de diabetes tipo 2. Achamos que precisamos de um número maior de voluntários para chegar a uma conclusão mais precisa.

Polimorfismos genéticos asociados a la respuesta del carcinoma de cabeza y cuello al cetuximab / Genetic polymorphisms associated with the response of head and neck carcinoma to cetuximab

Objetivo: Exponer los principales polimorfismos genéticos que han sido asociados a la respuesta del carcinoma de cabeza y cuello al cetuximab. Método: Se realizó una revisión no exhaustiva de artículos publicados en el período de enero de 2000 a diciembre de 2022, para ello se emplearon las bases de datos Medline (vía Pubmed) y Science Direct. En la evaluación de la calidad metodológica de los artículos incluidos se utilizó la guía para los estudios de asociación genética (Q-Genie). Resultados: Se identificaron un total de 206 artículos, de los cuales 12 cumplieron con los criterios para el análisis final. Se reportaron varios polimorfismos, tales como: EGFR-R521K (AA/GA), FcγRIIIa (158VV) y FcγRIIa (131HH), KRASLCS6 (TG/GG), AKT2:rs8100018, PTEN: rs12569998 en sus variantes mutadas, HIF-1α (CT/TT) y XRCC5 (GG/AA) que se asociaron con las variables de supervivencia, riesgo de progresión, tiempos hasta la progresión de la enfermedad, así como toxicidad cutánea. Conclusiones: Varios polimorfismos pueden asociarse con la respuesta del carcinoma de cabeza y cuello al tratamiento con cetuximab, siendo EGFR-R521K y FcγR IIIa-V158F los más estudiados. La enorme incertidumbre de los resultados alcanzados no permite alcanzar conclusiones firmes sobre la influencia de los polimorfismos genéticos en la respuesta al cetuximab; sin embargo, pueden convertirse en biomarcadores farmacogenéticos en la práctica clínica como una valiosa herramienta en la medicina personalizada, para predecir la respuesta medicamentosa. Para ello se requiere la realización de ensayos controlados con estratos por genotipo, con asignación aleatoria del tratamiento y el análisis de otras variables con valor pronóstico conocido.(AU)

Objective: To present the main genetic polymorphisms that have been associated with the response of head and neck carcinoma to cetuximab. Method: A non-exhaustive review of articles published in the period from January 2000 to December 2022 was carried out, for this purpose the Medline (via Pubmed) and Science Direct databases were used. The guide for genetic association studies (Q-Genie) was used to evaluate the methodological quality of the included articles. Results: A total of 206 articles were identified, of which 12 met the criteria for the final analysis. Several polymorphisms were reported, such as: EGFR-R521K (AA/GA), FcγRIIIa (158VV) and FcγRIIa (131HH), KRAS-LCS6 (TG/GG), AKT2:rs8100018, PTEN: rs12569998 in its mutated variants, HIF- 1α (CT/TT) and XRCC5 (GG/AA) that were associated with survival variables, risk of progression, times to disease progression, as well as skin toxicity. Conclusions: Several polymorphisms can be associated with the response of head and neck carcinoma to treatment with cetuximab, being EGFR-R521K and FcγR IIIa-V158F the most studied. The enormous uncertainty of the results obtained does not allow firm conclusions to be reached about the influence of genetic polymorphisms on the response to cetuximab; however, they can become pharmacogenetic biomarkers in clinical practice as a valuable tool in personalized medicine, to predict drug response. This requires carrying out controlled trials with strata by genotype, with random assignment of treatment and the analysis of other variables with known prognostic value.(AU)

Strong association between angiotensin-converting enzyme gene InDel polymorphism and COVID-19 diseases / Fuerte asociación entre el polimorfismo InDel del gen de la enzima convesiva de angiotensina y las enfermedades por COVID-19

Background and ObjectivesThe COVID-19 pandemic that emerged in China in late 2019 and spread rapidly around the world. There is evidence that COVID-19 infection can be influenced by genetic variations in the host. The aim of this study was to investigate the association between ACE InDel polymorphism and COVID-19 in Northern Cyprus.Patients and methodsThis study included 250 patients diagnosed with COVID-19 and 371 healthy controls. Genotyping for the ACE InDel gene polymorphism was performed by polymerase chain reaction.ResultsThe frequency of ACE DD homozygotes was significantly increased in COVID-19 patients compared to the control group (p=0.022). The difference in the presence of the D allele between the patient and control groups was statistically significant (57.2% and 50.67%, respectively, p<0.05). Individuals with the genotype II were found to have a higher risk of symptomatic COVID-19 (p=0.011). In addition, chest radiographic findings were observed more frequently in individuals with the genotype DD compared to individuals with the genotypes ID and II (p=0.005). A statistically significant difference was found when the time of onset of symptoms for COVID-19 and duration of treatment were compared with participants’ genotypes (p=0.016 and p=0.014, respectively). The time of onset of COVID-19 was shorter in individuals with the genotype DD than in individuals with the genotype II, while the duration of treatment was longer.ConclusionIn conclusion, the ACE I/D polymorphism has the potential to predict the severity of COVID-19. (AU)

Antecedentes y objetivosLa pandemia de COVID-19 surgió en China a fines de 2019 y se extendió rápidamente por todo el mundo. Existe evidencia de que la infección por COVID-19 puede verse influenciada por variaciones genéticas en el huésped. El objetivo de este estudio fue investigar la asociación entre el polimorfismo ACE InDel y COVID-19 en el norte de Chipre.Pacientes y métodosSe incluyeron 250 pacientes diagnosticados de COVID-19 y 371 controles sanos. El genotipado del polimorfismo del gen ACE InDel se realizó mediante reacción en cadena de la polimerasa.ResultadosLa frecuencia de homocigotos ACE DD aumentó significativamente en pacientes con COVID-19 en comparación con el grupo de control (p=0,022). La diferencia en la presencia del alelo D entre los grupos de pacientes y control fue estadísticamente significativa (57,2% y 50,67%, respectivamente, p<0,05). Las personas con el genotipo II tenían un mayor riesgo de COVID-19 sintomático (p=0,011). Además, los hallazgos radiográficos de tórax se observaron con mayor frecuencia en individuos con el genotipo DD en comparación con los individuos con los genotipos ID y II (p=0,005). Se encontró una diferencia estadísticamente significativa cuando se comparó el tiempo de aparición de los síntomas de COVID-19 y la duración del tratamiento con los genotipos de los participantes (p=0,016 y p=0,014, respectivamente). El tiempo de aparición de COVID-19 fue más corto en individuos con genotipoDD que en individuos con genotipoII, mientras que la duración del tratamiento fue más prolongada.ConclusionesEl polimorfismo ACE I/D podría predecir la gravedad de la COVID-19. (AU)

Identificación de polimorfismos obesogénicos en mexicanos / Identification of obesogenic polymorphisms in Mexicans

Introducción. La obesidad es una enfermedad metabólica caracterizada por el aumento del índice de la masa corporal. El riesgo de obesidad depende de factores ambientales, del estilo de vida y de la presencia de variantes genéticas originadas por mutaciones únicas y polimorfismos de un solo nucleótido (SNPs). Estudios han mostrado la importancia de la etnia en la heredabilidad de las variantes genéticas asociadas al desarrollo de la obesidad. En México, la prevalencia de sobrepeso y la obesidad es del 38.8 % y 32.4 %, respectivamente. Objetivo. El objetivo de este estudio es determinar SNPs que influyen de manera distintiva en el desarrollo de la obesidad de mexicanos. Materiales y métodos. Se realizó un estudio bibliográfico en la base de datos Pubmed con 70 artículos que estudian la asociación de diferentes SNPs con el desarrollo de la obesidad en mexicanos. Resultados. Se identifican los SNPs rs17782313 (MC4R), rs6548238 (TMEM18), rs6265 (BDNF) y rs7488665 (SH2B1) con un comportamiento diferencial respecto a los resultados obtenidos en población caucásica y el SNPs rs6232 del gen PCSK1 asociado con la aparición de la obesidad en edades juveniles en la población mexicana. Conclusiones. Concluyendo que la caracterización detallada de los genes de mayor incidencia en las distintas etnias contribuye a establecer estrategias personalizadas en particular de la población mexicana y que permitan desarrollar un sistema de alta sensibilidad para determinar la susceptibilidad a la obesidad(AU)

Introduction. Obesity is a metabolic disease characterized by an increase in the body mass index. The risk of obesity depends on environmental factors, lifestyle and the presence of genetic variants caused by single mutations and single nucleotide polymorphisms (SNPs). Studies have shown the importance of ethnicity in the heritability of genetic variants associated with the development of obesity. In Mexico, the prevalence of overweight and obesity is 38.8% and 32.4%, respectively. Objective. The objective of this study is to determine SNPs that have a distinctive influence on the development of obesity in Mexicans. Materials and Methods. A bibliographical study was carried out in the Pubmed database and 70 papers were found that study the association of different SNPs with the development of obesity in Mexicans. Results. The SNPs rs17782313 (MC4R), rs6548238 (TMEM18), rs6265 (BDNF) and rs7488665 (SH2B1) with a differential behavior with respect to the results obtained in the Caucasian population, and the SNPs rs6232 of the PCSK1 gene associated with the appearance of obesity in youth in the Mexican population. Conclusions. Concluding that the detailed characterization of the genes with the highest incidence in the different ethnic groups contributes to establish personalized strategies in particular of the Mexican population and that allow the development of a highly sensitive system to determine susceptibility to obesity(AU)

Performance of the tetra-primer PCR technique compared to PCR-RFLP in the search for rs12979860 (C/T) and rs8099917 (T/G) single nucleotide polymorphisms (SNPs) in the IFNL4 gene / Desempenho da técnica tetra-primer PCR em relação a PCR-RFLP na pesquisa de polimorfismos de nucleotídeos únicos (SNPs) rs12979860 (C/T) e rs8099917 (T/G) no gene IFNL4

Single nucleotide polymorphisms (SNPs, rs12979860 e rs8099917) in the Interferon Lambda 4 gene (IFNL4, formerly IFNL3and/or IL28B) has been associated with failure in the innate immune response, sustained virological response in hepatitis C, and HTLV-1-associated myelopathy (HAM) development. To search for these polymorphisms several methodologies can be employed, such as sequencing, real-time or quantitative polymerase chain reaction (qPCR), restriction fragment length polymorphism analysis in PCR products (PCR-RFLP), and tetra-primer PCR. The present study compared the performance of the tetra-primer PCR in relation to the PCR-RFLP, both optimized in the Research HTLV Laboratory of the Center of Immunology of Instituto Adolfo Lutz in São Paulo. One hundred DNA samples obtained from patients of STD/Aids Reference Centre in São Paulo, previously analyzed for IL28B SNPs by PCR-RFLP were selected for analysis, after confirming that they represent all IL28B SNPs patterns described in the literature. The results obtained showed concordance between the PCR-RFLP and the tetra-primer PCR SNPs results, and because of the low cost, easy to perform, and minor employment of biological specimen and reagents, the tetra-primer PCR is of choice to be used in routine. (AU)

Polimorfismos de nucleotídeos únicos (single nucleotide polymorphisms, SNPs rs12979860 e rs8099917) no gene que codifica o Interferon Lambda 4 (IFNL4, antigamente IFNL3 e/ou IL28B) têm sido associados às falhas na resposta imune inata e resposta virológica sustentada na hepatite C, e a mielopatia associada ao HTLV-1 (HTLV-1-associated myelopathy, HAM). A pesquisa destes polimorfismos pode empregar diversas metodologias: sequenciamento, reação em cadeia da polimerase em tempo real ou quantitativa (quantitative polymerase chain reaction, qPCR), análise de fragmentos de restrição enzimática em produtos de PCR (restriction fragment length polymorphism in PCR products, PCR-RFLP) e a tetra-primer PCR. Este estudo comparou o desempenho da tetra-primer PCR em relação a PCR-RFLP, ambas otimizadas no Laboratório de Pesquisa em HTLV do Centro de Imunologia do Instituto Adolfo Lutz de São Paulo. Foram selecionadas 100 amostras de DNA obtidas de pacientes do Centro de Referência e Treinamento em DST/Aids de São Paulo cujos SNPs na IL28B foram anteriormente determinados por PCR-RFLP e representaram todos os perfis descritos em literatura. Os resultados obtidos mostraram concordância entre elas, e pelo fato da tetra-primer PCR ter menor custo, ser de fácil execução, empregar menos tempo, insumos e material biológico, é a técnica de escolha para uso em rotina. (AU)

Strong association between angiotensin-converting enzyme gene InDel polymorphism and COVID-19 diseases.

BACKGROUND AND OBJECTIVES: The COVID-19 pandemic that emerged in China in late 2019 and spread rapidly around the world. There is evidence that COVID-19 infection can be influenced by genetic variations in the host. The aim of this study was to investigate the association between ACE InDel polymorphism and COVID-19 in Northern Cyprus. PATIENTS AND METHODS: This study included 250 patients diagnosed with COVID-19 and 371 healthy controls. Genotyping for the ACE InDel gene polymorphism was performed by polymerase chain reaction. RESULTS: The frequency of ACE DD homozygotes was significantly increased in COVID-19 patients compared to the control group (p=0.022). The difference in the presence of the D allele between the patient and control groups was statistically significant (57.2% and 50.67%, respectively, p<0.05). Individuals with the genotype II were found to have a higher risk of symptomatic COVID-19 (p=0.011). In addition, chest radiographic findings were observed more frequently in individuals with the genotype DD compared to individuals with the genotypes ID and II (p=0.005). A statistically significant difference was found when the time of onset of symptoms for COVID-19 and duration of treatment were compared with participants' genotypes (p=0.016 and p=0.014, respectively). The time of onset of COVID-19 was shorter in individuals with the genotype DD than in individuals with the genotype II, while the duration of treatment was longer. CONCLUSION: In conclusion, the ACE I/D polymorphism has the potential to predict the severity of COVID-19.

Genetic risk score for common obesity and anthropometry in Spanish schoolchildren.

IntroductionCommon or non-syndromic obesity is a complex polygenic trait conditioned by biallelic or single-base polymorphisms called SNPs (Single-Nucleotide Polymorphisms) that present an additive effect and act synergistically. Most genotype-obese phenotype association studies include body mass index (BMI) or waist-to-height ratio (WtHR), and very few introduce a broad anthropometric profile. ObjectiveTo verify whether a genetic risk score (GRS) developed from 10 SNPs is associated with the obesity phenotype assessed from anthropometric measures indicative of excess weight, adiposity and fat distribution. Material and methodsA series of 438 Spanish schoolchildren (6-16 years old) were evaluated anthropometrically (weight, height, waist circumference, skinfold thickness, BMI, WtHR, body fat percentage [%BF]). Ten SNPs were genotyped from saliva samples, generating a GRS for obesity, establishing genotype-phenotype association. ResultsSchoolchildren categorised as obese by BMI, ICT and %BF had higher GRS than their non-obese peers. The prevalence of overweight and adiposity was higher in subjects with a GRS above the median. Similarly, between 11 and 16 years of age, all anthropometric variables presented higher averages. ConclusionsGRS estimated from the 10 SNPs can be a diagnostic tool for the potential risk of obesity in Spanish schoolchildren and could be useful from the preventive perspective.

Polymorphism in cytolytic pathway genes in patients with pediatric inflammatory multisystemic syndrome temporally associated with SARS-CoV-2 / Polimorfismos em genes da via citolítica em pacientes com síndrome inflamatória multissistêmica pediátrica temporariamente associada ao SARS-CoV-2

Introduction: Pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS) is a systemic hyperinflammatory disease that occurs in a small number of children after being infected with SARS-CoV-2. Macrophage activation syndrome, an aggressive condition characterized by the excessive inflammation and activation of well-differentiated macrophages, has been shown to occur in patients infected by SARS-CoV-2. Considering the clinical and pathophysiological similarities between these diseases, our main objective was to determine whether gene polymorphisms associated with macrophage activation syndrome were also present in patients with PIMS-TS. Methods: DNA from 10 pediatric patients with PIMS-TS (case group) and ten COVID-19 patients without PIMS-TS (control group) were genotyped by Real-time PCR analysis (TaqMan®) for single nucleotide polymorphisms (SNP) in four genes associated with macrophage activation syndrome: perforin 1 (PRF1), granzyme B (GZMB), syntaxin 11 (STX11), and syntaxin binding protein 2 (STXBP2). The SNP analysis was performed using the additive, dominant, and recessive models. Results: A significantly higher frequency of an SNP (C wild allele in rs6573910) in the GZMB gene was observed in both the additive and dominant models in the PIMS-TS group than controls. A borderline significant difference was also observed for the G allele in rs7764017 of the STX11 gene in the PIMS-TS group in the additive model. Conclusions: This study indicated the presence of two polymorphisms in genes associated with macrophage activation syndrome (GZMB and STX11) in patients who developed PIMS-TS. If the presence of these SNPs is validated in a larger number of PIMS-TS cases, they can be used as potential biomarkers for early identification of pediatric patients with a higher probability of developing PIMS-TS associated with SARS-CoV-2 infection.

Introdução: A síndrome multissistêmica inflamatória pediátrica temporariamente associada ao SARS-CoV-2 (SIMP-TS) é uma doença hiperinflamatória sistêmica que ocorre em um pequeno número de crianças após serem infectadas pelo SARS-CoV-2. A síndrome de ativação de macrófagos (SAM), uma condição agressiva caracterizada pela inflamação excessiva e ativação de macrófagos bem diferenciados, demonstrou ocorrer em pacientes infectados por SARS-CoV-2. Considerando as semelhanças clínicas e fisiopatológicas entre essas doenças, neste estudo o nosso principal objetivo foi determinar se polimorfismos gênicos associados à SAM também estavam presentes em pacientes com SIMP-TS. Métodos: DNA de dez pacientes pediátricos com SIMP (grupo caso) e dez pacientes COVID-19 sem SIMP (grupo controle) foram genotipados por análise de PCR em tempo real (tecnologia TaqMan®) para polimorfismos de nucleotídeo único (SNPs) em quatro genes selecionados associados com SAM: perforina 1 (PRF1), granzima B (GZMB), sintaxina 11 (STX11) e proteína de ligação de sintaxina 2 (STXBP2). A análise dos SNPs foi realizada utilizando o modelo aditivo, dominante e recessivo. Resultados: Uma frequência significativamente maior de um SNP (alelo selvagem C em rs6573910) no gene GZMB foi observada pelos modelos aditivo e dominante no grupo SIMP quando comparado aos controles. Além disso, uma significância limítrofe foi observada para o alelo G em rs7764017 do gene STX11 no grupo SIMP pelo modelo aditivo. Conclusões: Nosso estudo indicou a presença de dois polimorfismos em genes associados à SAM (GZMB e STX11) em pacientes que desenvolveram SIMP-TS. Uma vez validada a presença desses SNPs em um número maior de casos de SIMP-TS, eles podem ser usados como potenciais biomarcadores para a identificação precoce de pacientes pediátricos com maior probabilidade de desenvolver SIMP-TS associado à infecção por SARS-CoV-2.

Helicobacter pylori infection: A balance between bacteria and host / Helicobacter pylori: un balance entre bacterias y huésped

Abstract In Argentina, despite the important studies conducted on the prevalence of infection and the antibiotic resistance of Helicobacter pylori, there are no reports simultaneously analyzing a profile of virulence factors of the bacterium and polymorphisms in cytokine genes in patients with different alterations in the gastric mucosa (including intestinal metaplasia, IM). Our aim was to evaluate H. pylori genotypes in 132 adult patients with chronic gastritis presenting three different histological findings (inactive chronic gastritis, active chronic gastritis IM( and active chronic gastritis IM+) along with SNP-174 G>C in the IL-6 gene. cagA, vacA and babA2 genes were analyzed by multiplex PCR. The -174 G>C SNP IL-6 gene was analyzed by PCR-RFLP. Patients with active chronic gastritis IM+ showed the highest proportion of the cagA(+)/IL-6GG, cagA(+)/vacAm1s1/IL-6GG and cagA(+)/vacAm1s1/babA2(+)/IL-6GG combinations (p<0.05). There was 4-5 times greater probability of finding patients presenting the GG genotype for SNP-174 G>C IL-6, which in turn were infected with the most virulent H. pylori genotypes -cagA(+), cagA(+)/vacAm1s1 and cagA(+)/vacAm1s1/babA2- in the ACGIM+ group in comparison to the ICG group. Our results provide regional data to the idea that the transition towards severe alterations in the gastric mucosa would be the result of a balance between specific factors of H. pylori and inherent host factors. This fact can be useful to identify patients at greater risk and to select those individuals requiring appropriate eradication treatment to prevent progression to gastric cancer.

Resumen En Argentina, a pesar de los importantes estudios realizados sobre la prevalencia de infección y la resistencia a antibióticos de Helicobacter pylori, no existen reportes que analicen simultáneamente un perfil de factores de virulencia de la bacteria y polimorfismos en genes de citoquinas en pacientes con diferentes alteraciones en la mucosa gástrica (incluida la metaplasia intestinal [MI]). Nuestro objetivo fue evaluar genotipos de H. pylori en 132 pacientes adultos con gastritis crónica, con tres diferentes hallazgos histológicos (gastritis crónica inactiva [GCI], gastritis crónica activa [MI(] y gastritis crónica activa [MI+]), junto con el SNP-174 G>C en el gen de IL- 6. Los genes cagA, vacA y babA2 se analizaron mediante PCR multiplex. El SNP-174 G>C IL-6 se analizó mediante PCR-RFLP. Los pacientes con gastritis crónica activa MI+ mostraron la mayor proporción de combinaciones cagA(+)/IL-6GG, cagA(+)/vacAm1s1/IL-6GG y cagA(+)/vacAm1s1/babA2(+)/IL-6GG (p<0,05). Hubo 4-5 veces mayor probabilidad de encontrar pacientes con el genotipo GG en SNP-174 G>C IL-6 y a su vez infectados con los genotipos más virulentos de H. pylori-cagA(+), cagA(+)/vacAm1s1 y cagA(+)/vacAm1s1/babA2-en el grupo gastritis crónica activa MI+ en comparación con el grupo GCI. Nuestros resultados aportan datos regionales a la idea de que la transición hacia alteraciones más graves en la mucosa gástrica resultaría de un equilibrio entre factores específicos de H. pylori y factores inherentes al huésped. Esto puede ser útil para identificar pacientes con mayor riesgo y seleccionar aquellos individuos que requieran un apropiado tratamiento de erradicación para prevenir la progresión al cáncer gástrico.

Role of HLA-DQB1 alleles in the risk, signs and symptoms, and severity of celiac disease in a Venezuelan population.

INTRODUCTION AND AIMS: Celiac disease (CD) is a complex condition, whose main genetic determinant involves HLA molecules, specifically the HLA-DQ2 and/or HLA-DQ8 heterodimers. Nevertheless, the frequency of the alleles encoding those molecules has not been reported in Venezuelan celiac patients. Therefore, the aim of our study was to evaluate the frequency of the HLA-DQB1 alleles in individuals with symptoms suggestive of CD and define the diagnostic markers of the condition in a Venezuelan population. MATERIAL AND METHODS: A cross-sectional study included 516 individuals with symptoms suggestive of CD. Molecular typing of the HLA-DQB1 locus was performed using a polymerase chain reaction-sequence-specific oligonucleotide procedure (PCR-SSO). RESULTS: A total of 58.3% of the individuals with clinical manifestations consistent with CD presented with at least one risk allele (DQB1*0201 and/or DQB1*0302), and the diagnosis was confirmed in 40 of them. The patients with CD had a higher frequency of the DQB1*0201 risk allele (26.25%), followed by the DQB1*0302 (17.5%) allele. There was an association between the presence of risk alleles and the presence of lesions characteristic of CD (P = 0.001), and a correlation was found between the genetic predisposition to develop CD and the presence of anti-tissue transglutaminase antibodies (P = 0.0127). CONCLUSIONS: The results support the role of the DQB1*02 and DQB1*0302 alleles in CD susceptibility and the histologic alterations of the intestinal mucosa, in a Venezuelan population.

Helicobacter pylori infection: A balance between bacteria and host.

In Argentina, despite the important studies conducted on the prevalence of infection and the antibiotic resistance of Helicobacter pylori, there are no reports simultaneously analyzing a profile of virulence factors of the bacterium and polymorphisms in cytokine genes in patients with different alterations in the gastric mucosa (including intestinal metaplasia, IM). Our aim was to evaluate H. pylori genotypes in 132 adult patients with chronic gastritis presenting three different histological findings (inactive chronic gastritis, active chronic gastritis IM- and active chronic gastritis IM+) along with SNP-174 G>C in the IL-6 gene. cagA, vacA and babA2 genes were analyzed by multiplex PCR. The -174 G>C SNP IL-6 gene was analyzed by PCR-RFLP. Patients with active chronic gastritis IM+ showed the highest proportion of the cagA(+)/IL-6GG, cagA(+)/vacAm1s1/IL-6GG and cagA(+)/vacAm1s1/babA2(+)/IL-6GG combinations (p<0.05). There was 4-5 times greater probability of finding patients presenting the GG genotype for SNP-174 G>C IL-6, which in turn were infected with the most virulent H. pylori genotypes -cagA(+), cagA(+)/vacAm1s1 and cagA(+)/vacAm1s1/babA2- in the ACGIM+ group in comparison to the ICG group. Our results provide regional data to the idea that the transition towards severe alterations in the gastric mucosa would be the result of a balance between specific factors of H. pylori and inherent host factors. This fact can be useful to identify patients at greater risk and to select those individuals requiring appropriate eradication treatment to prevent progression to gastric cancer.

El gen del receptor cannabinoide tipo 2 se asocia con la comorbilidad entre esquizofrenia y dependencia de cannabis y el gen de la enzima amidohidrolasa de ácidos grasos se asocia con la dependencia de cannabis en población española / Cannabinoid receptor type 2 gene is associated with comorbidity of schizophrenia and cannabis dependence and fatty acid amide hydrolase gene is associated with cannabis dependence in the Spanish population

El sistema cannabinoide se ha asociado con varios trastornos psiquiátricos como la esquizofrenia y las adicciones. Diversos estudios hanobservado que algunos polimorfismos del receptor cannabinoide tipo2 (CNR2), del receptor cannabinoide tipo 1 (CNR1) y del gen de la enzima amido hidrolasa de ácidos grasos (FAAH) pueden ser factores deriesgo de estos trastornos. Hemos analizado diversos polimorfismos delsistema cannabinoide en pacientes diagnosticados de esquizofrenia sintrastorno por uso de sustancias (n = 379), esquizofrenia con trastornopor uso de cannabis (n = 124), dependientes de cannabis sin psicosisasociada (n = 71) y un grupo de control (316) procedentes de diversoshospitales y centros de asistencia sanitaria españoles. Hemos encontrado una asociación entre los polimorfismos rs35761398 y rs12744386 delCNR2 con la presencia de esquizofrenia y trastorno por uso de cannabis comórbido y una pérdida de heterocigosidad en el polimorfismors324420 del gen FAAH con la dependencia de cannabis en poblaciónespañola. Los polimorfismos rs35761398 y rs12744386 en CNR2 son factores de riesgo para esquizofrenia en sujetos dependientes de cannabis.La pérdida de heterocigosidad en el polimorfismo rs324420 en el genFAAH es un factor de riesgo para la dependencia de cannabis. (AU)

The endocannabinoid system has been associated with various psychiatric disorders, such as schizophrenia or addictive disorders. Recent studies have found that some polymorphisms in the cannabinoid receptortype 2 (CNR2), cannabinoid receptor type 1 (CNR1) and fatty acid amide hydrolase (FAAH) genes could play an important role as risk factorsin the etiology of these diseases. We analysed different cannabinoidgene polimorphisms from non-substance using patients diagnosed withschizophrenia (n = 379), schizophrenic patients with cannabis use disorders (n = 124), cannabis users who did not have psychoses (n = 71),and 316 controls from various Spanish hospitals and health centres.We found a statistical association between polymorphisms rs35761398and rs12744386 in the CNR2 gene and comorbidity of schizophreniaand cannabis dependence, as well as an association between loss ofheterozygosity (overdominance) for polymorphism rs324420 in theFAAH gene and cannabis dependence in a Spanish population sample.The rs35761398 and rs12744386 polymorphisms in the CNR2 gene aregenetic risk factors for schizophrenia in cannabis-dependent subjects.Loss of heterozygosity for polymorphism rs324420 in the FAAH gene isa genetic risk factor for cannabis dependence in this population. (AU)

Polimorfismo genético associado a doença renal crônica e periodontite: uma revisão sistemática de literatura / Genetic polymorphism associated with chronic kidney disease and periodontitis: a systematic literature review / Polimorfismo genético asociado a enfermedad renal crónica y periodontitis: una revisión sistemática de la literatura

A periodontite é uma doença infecto-inflamatória associada ao biofilme disbiótico que afeta os tecidos de proteção e de suporte dos dentes. O processo inflamatório que ocorre durante a periodontite tem sido associado à inflamação sistêmica em pacientes com doença renal crônica. Os polimorfismos genéticos são alterações no DNA que podem ter classificações diferentes dependendo da mutação gerada, e podem ser criados ou destruídos. Objetivo: O objetivo desta revisão sistemática da literatura foi elucidar a seguinte questão: os polimorfismos genéticos estão associados à doença renal crônica e à periodontite? Material e Métodos: A pesquisa foi realizada no PubMed, Biblioteca Cochrane, EMBASE, Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS), Bibliografia Brasileira de Odontologia (BBO), Biblioteca Virtual em Saúde (BVS), SciELO, Scopus, Web of Science e bases de dados de literatura cinzenta (Google Scholar) sem restrições de data ou idioma em 28 de junho de 2021 e atualizada em 26 de janeiro de 2023. Os descritores padronizados (Medical Subject Headings, MeSH) utilizados foram: "polimorfismo genético", "doença renal crônica" e "periodontite", de acordo com o banco de dados consultado, utilizando os operadores booleanos "AND". Resultado: 25 publicações foram identificadas. Após a análise do título, do resumo e do texto completo, 6 estudos de caso-controle foram selecionados para análise. Todos incluíam artigos investigando o papel de diferentes polimorfismos genéticos em ambas as doenças. Alguns genes apresentavam uma relação próxima com o perfil inflamatório que caracteriza ambas as doenças. Conclusão: Entre os polimorfismos estudados, os polimorfismos VNTR no gene IL4 e MCP-1-2518 A/G apresentaram uma associação positiva tanto com a periodontite quanto com a doença renal crônica. Entretanto, são necessários mais estudos para melhor compreensão do papel dos polimorfismos genéticos nessas doenças.

Periodontitis is an infectious-inflammatory disease associated with dysbiotic biofilm that affects the protective and supporting tissues of the teeth. The inflammatory process that occurs during periodontitis has been associated with systemic inflammation in patients with chronic kidney disease. Genetic polymorphisms are changes in DNA that can have different classifications depending on the mutation generated, and can be created or destroyed. Objective: The aim of this systematic review of the literature was to elucidate the following question: are genetic polymorphisms associated with chronic kidney disease and periodontitis? Material and Methods: The search was conducted in PubMed, Cochrane Library, EMBASE, Latin American and Caribbean Literature on Health Sciences (LILACS), Brazilian Bibliography of Dentistry (BBO), Virtual Health Library (VHL), SciELO, Scopus, Web of Science and gray literature databases (Google Scholar) without date or language restrictions on June 28, 2021 and updated on January 26, 2023. The standardized descriptors (Medical Subject Headings, MeSH) used were: "genetic polymorphism", "chronic kidney disease" and "periodontitis", according to the database consulted, using the Boolean operators "AND". Result: 25 publications were identified. After reviewing the title, abstract, and full text, 6 case-control studies were selected for analysis. All included articles investigating the role of different genetic polymorphisms in both diseases. Some genes showed a close relationship with the inflammatory profile that characterizes both diseases. Conclusion: Among the polymorphisms studied, the VNTR polymorphisms in the IL4 gene and MCP- 1-2518 A/G showed a positive association with both periodontitis and chronic kidney disease. However, further studies are needed to better understand the role of genetic polymorphisms in these diseases.

La periodontitis es una enfermedad infeccioso-inflamatoria asociada a un biofilm disbiótico que afecta a los tejidos protectores y de soporte de los dientes. El proceso inflamatorio que se produce durante la periodontitis se ha asociado con la inflamación sistémica en pacientes con enfermedad renal crónica. Los polimorfismos genéticos son cambios en el ADN que pueden tener diferentes clasificaciones dependiendo de la mutación generada, pudiendo ser creados o destruidos. Objetivo: El objetivo de esta revisión sistemática de la literatura fue dilucidar la siguiente pregunta: ¿están asociados los polimorfismos genéticos con la enfermedad renal crónica y la periodontitis? Material y Métodos: La búsqueda fue realizada en PubMed, Cochrane Library, EMBASE, Literatura Latinoamericana y del Caribe en Ciencias de la Salud (LILACS), Bibliografía Brasileña de Odontología (BBO), Biblioteca Virtual en Salud (BVS), SciELO, Scopus, Web of Science y bases de datos de literatura gris (Google Scholar) sin restricciones de fecha o idioma el 28 de junio de 2021 y actualizada el 26 de enero de 2023. Los descriptores normalizados (Medical Subject Headings, MeSH) utilizados fueron: "polimorfismo genético", "enfermedad renal crónica" y "periodontitis", según la base de datos consultada, utilizando los operadores booleanos "AND". Resultado: Se identificaron 25 publicaciones. Tras analizar el título, el resumen y el texto completo, se seleccionaron 6 estudios de casos y controles para su análisis. Todos los trabajos incluidos investigaban el papel de diferentes polimorfismos genéticos en ambas enfermedades. Algunos genes mostraron una estrecha relación con el perfil inflamatorio que caracteriza a ambas enfermedades. Conclusión: Entre los polimorfismos estudiados, los polimorfismos VNTR en el gen IL4 y MCP-1-2518 A/G mostraron una asociación positiva tanto con la periodontitis como con la enfermedad renal crónica. Sin embargo, se necesitan más estudios para comprender mejor el papel de los polimorfismos genéticos en estas enfermedades.

Por trás da leptina: uma revisão de literatura / Behind the leptin: a literature review / Detrás de leptin: una revisión de la literatura

A obesidade é uma doença crônica, multifatorial, que afeta todas as idades e classes sociais. Esta comorbidade tem avançado em decorrência de diversos fatores e sua prevalência está ancorada em diferentes dimensões como as biológicas, sociais, históricas, comportamentais, saúde pública e política. O presente estudo tem como objetivo caracterizar o gene da leptina, seu produto e de seus receptores, assim como os mecanismos que corroboram com o desenvolvimento da obesidade e seu envolvimento com distúrbios alimentares. A leptina é uma proteína secretada principalmente nos adipócitos, ela reduz o apetite por meio da inibição da formação de neuropeptídeos relacionados ao apetite, como o neuropeptídeo Y e eleva a expressão de neuropeptídeos anorexígenos, como o hormônio liberador de corticotropina, por isso que os altos níveis de leptina reduzem a ingestão alimentar, em contraste com os níveis baixos que induzem hiperfagia. Como a leptina realiza o controle da saciedade e regulação do gasto energético, o indivíduo com disfunção neste gene não desenvolve essa função corretamente. Isso se deve aos SNPs, que de acordo com estudos aumentam a susceptibilidade à obesidade. Além do mais, a leptina pode estar envolvida com processo patológico de alguns distúrbios alimentares, predispondo o paciente às condições como anorexia nervosa e bulimia.

Obesity is a chronic, multifactorial disease that affects all ages and social classes. This comorbidity has advanced as a result of several factors and its prevalence is anchored in different dimensions such as biological, social, historical, behavioral, public health and political. The present study aims to characterize the leptin gene, its product and its receptors, as well as the mechanisms that corroborate the development of obesity and its involvement with eating disorders. Leptin is a protein secreted mainly in adipocytes, it reduces appetite by inhibiting the formation of appetite-related neuropeptides such as neuropeptide Y and elevates the expression of anorexic neuropeptides such as corticotropin-releasing hormone, so high levels of leptin reduce dietary intake, in contrast to low levels that induce hyperphagia. As leptin performs satiety control and regulation of energy expenditure, the individual with dysfunction in this gene does not develop this function properly. This is due to SNPs, which according to studies increase susceptibility to obesity. Furthermore, leptin may be involved with the pathological process of some eating disorders, predisposing the patient to conditions such as anorexia nervosa and bulimia.

La obesidad es una enfermedad crónica multifactorial que afecta a todas las edades y clases sociales. Esta comorbilidad ha avanzado como resultado de diversos factores y su prevalencia está anclada en diferentes dimensiones, como la biológica, la social, la histórica, la conductual, la salud pública y la política. El objetivo de este estudio es caracterizar el gen de la leptina, su producto y sus receptores, así como los mecanismos que corroboran el desarrollo de la obesidad y su participación en los trastornos alimentarios. La leptina es una proteína secretada principalmente en los adipocitos, reduce el apetito inhibiendo la formación de neuropéptidos relacionados con el apetito, como el neuropéptido Y y eleva la expresión de neuropéptidos anorexógenos, como la hormona que libera la corticotropina, razón por la cual los altos niveles de leptina reducen la ingesta dietética, en contraste con los bajos niveles inducir hiperagia. Como la leptina lleva a cabo el control de la saciedad y la regulación del gasto energético, el individuo con disfunción en este gen no desarrolla esta función correctamente. Esto se debe a los SNP, que según los estudios aumentan la susceptibilidad a la obesidad. Además, la leptina puede estar implicada en el proceso patológico de algunos trastornos alimentarios, predisponiéndose al paciente a condiciones tales como anorexia nerviosa y bulimia.

Cáncer colorrectal. Variantes génicas en la vía de señalización BMP y ancestría en población mexicana / Colorectal cancer. Genetic variants in BMP signaling pathway and ancestry in the Mexican population

Resumen Introducción: Variantes génicas relacionadas con la vía de señalización de las proteínas morfogenéticas óseas (BMP2, BMP4, GREM1, SMAD7) se han asociado a cáncer colorrectal, principalmente en poblaciones caucásicas. Objetivo: Describir la asociación de variantes en miembros de la vía BMP en población mexicana, caracterizada por su ancestría indoamericana y caucásica. Métodos: Se realizó el genotipado de 1000 casos de cáncer colorrectal y 1043 individuos de control reclutados en la Ciudad de México, Monterrey y Torreón mediante la plataforma Sequenom. Con análisis univariados y multivariados se estudiaron las asociaciones entre cáncer colorrectal y variantes. Resultados: Las variantes rs4444235, rs12953717 y rs4939827 replicaron la asociación con la neoplasia (p ≤ 0.05). La ascendencia caucásica mostró asociación con el tumor. Conclusiones: El estudio mostró las asociaciones entre cáncer colorrectal y las variantes SMAD7 y BMP4, así como con el componente caucásico de la mezcla étnica.

Abstract Introduction: Genetic variants related to bone morphogenetic proteins (BMP2, BMP4, GREM1, SMAD7) signaling pathway have been associated with colorectal cancer, mainly in Caucasian populations. Objective: To describe the association of variants in members of the BMP signaling pathway in a Mexican population, characterized by its indigenous American and Caucasian ancestry. Methods: Genotyping of 1,000 colorectal cancer cases and 1,043 control individuals recruited in Mexico City, Monterrey, and Torreón was carried out using the Sequenom platform. Associations between colorectal cancer and variants were studied with univariate and multivariate analyses. Results: Variants rs4444235, rs12953717 and rs4939827 replicated the association with the neoplasm (p ≤ 0.05). Caucasian ancestry showed association with the tumor. Conclusions: The study replicated the associations between colorectal cancer and SMAD7 and BMP4 variants, with an association being observed with the Caucasian component of the ethnic mix.

Variability of PDYN and OPRK1 genes in four argentinian populations and its genetic association with clinical variables related to acute postsurgical pain / Variabilidad de los genes PDYN y OPRK1 en cuatro poblaciones argentinas y su asociación con variables clínicas relacionadas al dolor agudo post-quirúrgico

ABSTRACT Several population studies showed an association between variation in pain sensitivity and genetic polymorphisms located in Prodynorphin (PDYN) and Kappa Opioid Receptor (OPRK1) human genes. We analysed polymorphisms of these two genes to characterise their variation in Argentinian populations, as well as to evaluate their association with acute pain sensitivity. We studied 11 genetic markers in individuals from four locations in Argentina (Ciudad Autónoma de Buenos Aires, La Plata, Resistencia, and Misión Nueva Pompeya), calculated the population parameters, and evaluated the possible association among pain sensitivity, clinical, and genetic variables through a Generalised Estimating Equation model. High linkage disequilibrium was observed in the four populations for both genes, and significant differences were found among frequencies of Argentinian populations and those from other continents reported in the 1000 Genomes Project. Four PDYN gene polymorphisms from 3´ untranslated region and exon 4 showed association with acute pain sensitivity. One genotype of each of these polymorphisms was associated with a higher pain sensitivity, probably related with the activation of the N-methyl-D-aspartate (NMDA) receptors. We found a strong association with acute pain for the following clinical variables: 1) time after surgery, 2) intravenous klosidol supplied every 8 h, and 3) type of incision. Our results highlight the importance of a regional study of genetic variants which influence pain sensitivity and analgesic response.

RESUMEN La asociación entre la sensibilidad al dolor y los polimorfismos que presentan los genes humanos de prodinorfina (PDYN) y receptor opioide kappa (OPRK1) se ha evidenciado en distintos estudios poblacionales. Con el objetivo de caracterizar la variación de estos genes y evaluar su asociación con dolor agudo en la población argentina, analizamos 11 polimorfismos en individuos provenientes de cuatro localidades argentinas (Ciudad Autónoma de Buenos Aires, La Plata, Resistencia, y Misión Nueva Pompeya). Calculamos los parámetros poblacionales y evaluamos la posible asociación entre sensibilidad al dolor, variables clínicas y variables genéticas a través de un modelo de ecuación generalizada de estimación. Se observó alto desequilibrio de ligamiento para ambos genes en las cuatro poblaciones analizadas, y se encontraron diferencias significativas entre las frecuencias de poblaciones argentinas y las reportadas en el Proyecto 1000 Genomes para poblaciones de otros continentes. Cuatro polimorfismos de la región 3´UTR y el exón 4 de PDYN mostraron asociación con la sensibilidad al dolor agudo. En cada uno de estos polimorfismos, un genotipo resultó asociado con alta sensibilidad al dolor, probablemente en relación con la activación de receptores N-metil-D-aspartato (NMDA). Encontramos una fuerte asociación con dolor agudo para las siguientes variables clínicas: 1) tiempo post-cirugía, 2) administración intravenosa de klosidol cada 8 h, y 3) tipo de incisión. Nuestros resultados resaltan la importancia de realizar estudios regionales de variables genéticas que influyen en la sensibilidad al dolor y la respuesta analgésica.

[Vitamin D and polymorphisms of VDR and GC genes in the severity and mortality from COVID-19. A systematic review]. / Vitamina D y polimorfismos de los genes VDR y GC en la severidad y mortalidad por COVID-19. Una revisión sistemática.

Introduction: Previous studies have pointed to a possible relationship between vitamin D deficiency and the severity of the disease promoted by SARS-CoV-2, reducing respiratory and cardiovascular complications caused by a hyperreaction of the immune system known as "cytokine storm". This vitamin exerts multiple functions that depend on the presence and levels of different proteins, such as the vitamin D receptor (VDR) and the vitamin D binding protein (DBP), and the existence of single nucleotide polymorphisms (SNPs) of the genes that encode these proteins. The objective of this review is to assess whether some VDR and GC SNPs are risk factors for the most severe forms of COVID-19 disease and whether they condition the response to vitamin D supplementation. A search was performed in PubMed, Google Scholar and Scielo, finding that genotypes in patients affected by COVID-19, were rarely performed, although some studies find a relationship between different alleles and the severity of the disease. The ApaI polymorphism of the VDR gene stands out, as the minor allele "a" increases the risk of mortality from COVID-19 (OR = 11.828, CI: 2,493-56,104, p = 0.002). Results divergency in the efficacy of vitamin D supplementation suggest the need for a larger number of studies. In conclusion, the study of VDR and GC polymorphisms seems essential to effectively treat vitamin D deficiency and particularly to protect against COVID-19. Well-designed studies are needed to elucidate whether plasma vitamin D levels play a role of casuality or causality.

Introducción: Estudios previos han señalado una posible relación entre la deficiencia de la vitamina D y la severidad de la enfermedad promovida por el SARS-CoV-2, reduciendo las complicaciones respiratorias y cardiovasculares causadas por una respuesta exacerbada del sistema inmune. Esta vitamina ejerce múltiples funciones que dependen de la presencia y niveles de diferentes proteínas, como el receptor de la vitamina D (VDR) y la proteína de unión de la vitamina D (DBP), y de la existencia de polimorfismos de un solo nucleótido (SNP) de los genes que codifican a estas proteínas. El objetivo de esta revisión es evaluar si algunos SNP de VDR y GC son factores de riesgo de las formas más severas de la enfermedad COVID-19 y si condicionan la respuesta a la suplementación con vitamina D. Se realizó una búsqueda en PubMed, Google Scholar y Scielo, encontrándose que son escasos los genotipados en pacientes afectados por COVID-19, aunque algunos trabajos hallan una relación entre diferentes alelos y la severidad de la enfermedad. Destaca el polimorfismo ApaI del gen VDR, el cual alelo menor "a" aumenta el riesgo de mortalidad por COVID-19 (OR = 11,828, CI: 2.493-56.104, p = 0,002). La divergencia de resultados en la eficacia de la suplementación de vitamina D sugiere la necesidad de un mayor número de estudios. En conclusión, el estudio de polimorfismos VDR y GC resulta fundamental para tratar eficazmente la deficiencia de vitamina D y en particular en la protección frente a COVID-19. Se necesitan estudios bien diseñados para dilucidar si los niveles plasmáticos de vitamina D juegan un papel de casualidad o causalidad.

Asociación entre los polimorfismos genéticos de nucleótido único en genes transportadores ABC con la epilepsia farmacorresistente en la población española / Association between single nucleotide genetic polymorphisms in ABC transporter genes with drug-resistant epilepsy in the Spanish population

Introducción: El 30% de los pacientes con epilepsia no responde al tratamiento farmacológico. La presencia de polimorfismos genéticos de nucleótido único (SNP) en el individuo puede influir en la variabilidad de respuesta al tratamiento farmacológico. La hipótesis de transportadores plantea que la presencia de SNP en los genes que codifican las proteínas ABC repercutiría en la biodisponibilidad de los fármacos anticrisis en el foco epileptógeno, lo que ocasionaría refractariedad. El objetivo del presente estudio fue evaluar la asociación de 13 polimorfismos en los genes ABCB1, ABCC2, ABCC5 y ABCG2 con la epilepsia farmacorresistente (EFR) en población española. Sujetos y métodos: Se realizó un estudio de casos y controles que incluyó a 327 pacientes con epilepsia: 227 farmacorresistentes y 100 farmacocontrolados según los criterios de la Liga Internacional contra la Epilepsia. En el ADN de leucocitos de sangre periférica extraído se estudiaron los polimorfismos en los genes transportadores ABC. Se utilizó la plataforma tecnológica iPlex® Gold y Mass ARRAY. Se compararon las frecuencias alélicas y genotípicas del grupo de casos y del de controles, el valor de p, la odds ratio y los intervalos de confianza al 95%. Resultados: La frecuencia alélica y genotípica del presente estudio fue similar a la comunicada en las bases de datos poblacionales. En los SNP estudiados no se encontraron diferencias significativas (p > 0,05) en todos los modelos de herencia analizados. Conclusiones: Nuestros resultados sugieren que no existe asociación entre los polimorfismos analizados en los genes ABC con la EFR en población española. Sin embargo, otros estudios adicionales confirmarán o descartarán estos resultados.(AU)

Introduction: Almost a third of all patients with epilepsy (30%) fail to respond to pharmacological treatment. The presence of single nucleotide polymorphisms (SNPs) in the individual may influence the variability of the response to drug treatment. The transporter hypothesis posits that the presence of SNPs in the genes encoding ABC proteins would affect the bioavailability of antiseizure drugs at the epileptogenic focus, giving rise to refractoriness. The aim of the present study was to evaluate the association of 13 polymorphisms in the ABCB1, ABCC2, ABCC5 and ABCG2 genes with drug-resistant epilepsy (DRE) in a Spanish population. Subjects and methods: A case-control study was conducted involving 327 patients with epilepsy: 227 resistant to drug therapy and 100 in whom their medication enabled them to control their symptoms, according to International League Against Epilepsy criteria. In the peripheral blood leukocyte DNA that was extracted, polymorphisms in the ABC transporter genes were studied. The iPlex® Gold and Mass ARRAY technology platform was used. The allele and genotypic frequencies of the case and control groups, p-value, odds ratio and 95% confidence intervals were compared. Results: The allele and genotypic frequency of the present study was similar to that reported in population-based databases. For the SNPs studied, no significant differences (p > 0.05) were found in any of the inheritance models analysed. Conclusions: Our results suggest that there is no association between the polymorphisms analysed in the ABC genes and DRE in the Spanish population. Nevertheless, further studies will confirm or refute these results.(AU)

Vitamina D y polimorfismos de los genes VDR y GC en la severidad y mortalidad por COVID-19. Una revisión sistemática / Vitamin D and polymorphisms of VDR and GC genes in the severity and mortality from COVID-19. A systematic review

Estudios previos han señalado una posible relación entre la deficiencia de la vitamina D y la severidad de la enfermedad promovida por el SARS-CoV-2, reduciendo las complicaciones respiratorias y cardiovasculares causadas por una respuesta exacerbada del sistema inmune. Esta vitamina ejerce múltiples funciones que dependen de la presencia y niveles de diferentes proteínas, como el receptor de la vitamina D (VDR) y la proteína de unión de la vitamina D (DBP), y de la existencia de polimorfismos de un solo nucleótido (SNP) de los genes que codifican a estas proteínas. El objetivo de esta revisión es evaluar si algunos SNP de VDR y GC son factores de riesgo de las formas más severas de la enfermedad COVID-19 y si condicionan la respuesta a la suplementación con vitamina D. Se realizó una búsqueda en PubMed, Google Scholar y Scielo, encontrándose que son escasos los genotipados en pacientes afectados por COVID-19, aunque algunos trabajos hallan una relación entre diferentes alelos y la severidad de la enfermedad. Destaca el polimorfismo ApaI del gen VDR, el cual alelo menor “a” aumenta el riesgo de mortalidad por COVID-19 (OR = 11,828, CI: 2.493-56.104, p = 0,002). La divergencia de resultados en la eficacia de la suplementación de vitamina D sugiere la necesidad de un mayor número de estudios. En conclusión, el estudio de polimorfismos VDR y GC resulta fundamental para tratar eficazmente la deficiencia de vitamina D y en particular en la protección frente a COVID-19. Se necesitan estudios bien diseñados para dilucidar si los niveles plasmáticos de vitamina D juegan un papel de casualidad o causalidad. (AU)

Previous studies have pointed to a possible relationship between vitamin D deficiency and the severity of the disease promoted by SARS-CoV-2, reducing respiratory and cardiovascular complications caused by a hyperreaction of the immune system known as “cytokine storm”. This vitamin exerts multiple functions that depend on the presence and levels of different proteins, such as the vitamin D receptor (VDR) and the vitamin D binding protein (DBP), and the existence of single nucleotide polymorphisms (SNPs) of the genes that encode these proteins. The objective of this review is to assess whether some VDR and GC SNPs are risk factors for the most severe forms of COVID-19 disease and whether they condition the response to vitamin D supplementation. A search was performed in PubMed, Google Scholar and Scielo, finding that genotypes in patients affected by COVID-19, were rarely performed, although some studies find a relationship between different alleles and the severity of the disease. The ApaI polymorphism of the VDR gene stands out, as the minor allele “a” increases the risk of mortality from COVID-19 (OR = 11.828, CI: 2,493-56,104, p = 0.002). RESULTS divergency in the efficacy of vitamin D supplementation suggest the need for a larger number of studies. In CONCLUSION, the study of VDR and GC polymorphisms seems essential to effectively treat vitamin D deficiency and particularly to protect against COVID-19. Well-designed studies are needed to elucidate whether plasma vitamin D levels play a role of casuality or causality. (AU)