Genetic predisposition of BDNF (rs6265) gene is susceptible to Schizophrenia: A prospective study and updated meta-analysis.

INTRODUCTION: Genetic polymorphism in the BDNF gene has been found to cause neuronal alterations and has been identified as a causal factor for many neuropsychiatric disorders. Therefore, various neurological case-control studies and meta-analyses have been conducted to find the possible link between BDNF and susceptibility to schizophrenia. METHOD: This meta-analysis gathered data from 25 case-control studies including a total of 8384 patients with schizophrenia and 8821 controls in order to identify the relationship between the rs6265 single nucleotide polymorphism and the disease, evaluating the combined odds ratio and 95% confidence intervals under 5 different genetic models. Validation followed the "Leave one out" method, and we used the Egger test and Begg's funnel plot to identify publication bias. RESULTS: Research into the rs6265 (G/A) polymorphism revealed a non-significant association with schizophrenia in all 5 genetic models; in the subgroup analysis, no association was found between white and Asian populations, with a p value>.05. CONCLUSIONS: Overall, the updated meta-analysis revealed that rs6265 exonic polymorphisms do not increase susceptibility to this disease. However, to better understand the pathogenesis of the disease, there is a need for further case-control studies into the BDNF polymorphism including larger sample sizes and different ethnic groups.

Associations among SNPs in two addictive genes, food addiction, and antioxidant markers in recreationally active young women.

Introduction: Introduction: food addiction is associated with genetic polymorphisms and decreased antioxidant intake. Objectives: this study determined the associations among food addiction, dopamine receptor 2 (DRD2) and toll-interleukin 1 receptor (TIR) domain-containing adaptor protein (TIRAP rs625413) gene polymorphisms, antioxidant capacities, and zinc levels among recreationally active Turkish women. Methods: the Yale Food Addiction Scale was used to evaluate the food addiction status. Serum antioxidant capacities and zinc levels were evaluated by blood analyses. Deoxyribonucleic acid (DNA) extraction was performed using peripheral blood leukocytes, and the polymorphism status of the DRD2 Taq 1A and TIRAP genes was investigated using a commercial kit. Results: the frequencies of the heterozygous genotypes of DRD2 Taq 1A and TIRAP were 23.1 % and 31.4 %, respectively, and the frequency of risk allele homozygous genotypes was 3.2 %. Most participants (94.4 %) had a nonpolymorphic/wild (CC) genotype in both genes; however, 11.5 % of the participants had a food addiction. The differences between serum antioxidant capacities, zinc levels, and body mass indices of those with and without food addiction were statistically significant. However, there were no differences in the serum zinc and antioxidant levels among the different genotypes. Conclusion: food addiction in young Turkish women was not associated with DRD2 Taq 1A or TIRAP polymorphisms but was associated with serum antioxidant capacities and zinc levels. Further studies on different loci of the same genes or genotypes of different genes with larger sample sizes are warranted.

Introducción: Introducción: la adicción a la comida está asociada con polimorfismos genéticos y disminución de la ingesta de antioxidantes. Objetivos: este estudio determinó las asociaciones entre la adicción a la comida, los polimorfismos del gen de la proteína adaptadora que contiene el dominio del receptor de dopamina 2 (DRD2) y del receptor de interleucina 1 (TIR) (TIRAP rs625413), las capacidades antioxidantes y los niveles de zinc entre mujeres turcas recreativamente activas. Métodos: se utilizó la escala de adicción a la comida de Yale para evaluar el estado de adicción a la comida. Las capacidades antioxidantes séricas y los niveles de zinc se evaluaron mediante análisis de sangre. La extracción de ácido desoxirribonucleico (ADN) se realizó a partir de leucocitos de sangre periférica y el estado de polimorfismo de los genes DRD2 Taq 1A y TIRAP se investigó con un kit comercial. Resultados: las frecuencias de los genotipos heterocigotos de DRD2 Taq 1A y TIRAP fueron 23,1 % y 31,4 %, respectivamente, y la frecuencia de genotipos homocigotos de alelos de riesgo fue de 3,2 %. La mayoría de las participantes (94,4 %) tenían un genotipo no polimórfico/salvaje (CC) en ambos genes; sin embargo, el 11,5 % de las participantes tenía adicción a la comida. Las diferencias entre las capacidades antioxidantes séricas, los niveles de zinc y los índices de masa corporal de aquellas con y sin adicción a la comida fueron estadísticamente significativas. Sin embargo, no hubo diferencias en los niveles séricos de zinc y antioxidantes entre los diferentes genotipos. Conclusión: la adicción a la comida en mujeres jóvenes turcas no se asoció con los polimorfismos DRD2 Taq 1A o TIRAP, pero se asoció con las capacidades séricas antioxidantes y los niveles de zinc. Se justifican más estudios sobre diferentes loci de los mismos genes o genotipos de diferentes genes con tamaños de muestra más grandes.

Correlation between genetic polymorphisms in apolipoprotein E and atrial fibrillation.

This work explores correlations between genetic polymorphisms in apolipoprotein E (ApoE) and atrial fibrillation (AF). We detected polymorphisms in the APOE gene in 64 patients with AF and 49 non-AF volunteers at the Department of Cardiology of Lianyungang Second People's Hospital between July 2017 and July 2019. We found significant differences in age, body mass index, left atrial diameter, and left ventricular ejection fraction between the two groups. Six APOE genotypes were observed: ɛ2/ɛ2; ɛ2/ɛ3; ɛ2/ɛ4; ɛ3/ɛ3; ɛ3/ɛ4; and ɛ4/ɛ4. The ɛ3/ɛ3 genotype was significantly less frequent in the AF group than in the control group, while the ɛ3/ɛ4 and ɛ4/ɛ4 genotypes were significantly more frequent in the AF group than in the control group (p<0.05). ApoE3 penetrance was significantly lower in the AF group than in the control group (p<0.05), while ApoE4 penetrance was significantly higher in the AF group than in the control group (p<0.05). ApoE3 penetrance was significantly lower in the AF group than in the control group (p<0.05). Binary logistic regression analysis showed that age, body mass index, left atrial diameter, left ventricular ejection fraction, and ApoE4 were risk factors for AF. Finally, we found that ApoE polymorphisms impacted the occurrence of AF and that ApoE4 is an AF-sensitive phenotype.

Association between nutritional risk markers and polymorphisms rs2291166 in TJP1 and VNTR (CAG)n in ATXN2 in an obese adolescent Mexican population. / Asociación entre marcadores de riesgo nutricionales con los polimorfismos rs2291166 de TJP1 y el VNTR (CAG)n de ATXN2 en población mexicana adolescente con obesidad.

OBJECTIVE: To estimate the correlation between indices of diet quality (DQIs), insulin sensitivity (QUICKI) and resistance (HOMA-IR), waist circumference (WHR) and body mass (BMI) and the alleles and genotypes of the TJP1 SNP rs2291166 and the VNTR of ATXN2 in adolescent patients. SUBJECTS AND METHOD: The study enrolled 85 subjects aged 10-20years, from the city of Tuxtepec, Oaxaca, Mexico, recruited in the period 2017-2018. DQIs, BMI, WHR, HOMA-IR, QUICKI, and diet quality index were measured. The rs2291166 polymorphism in TJP1 was determined by allele-specific PCR and the (CAG)n expansion in ATXN2 was determined by hot start PCR. PCR products were analyzed using 8% PAGE electrophoresis and silver nitrate staining. RESULTS: A correlation was found of indices DQIs, HOMA-IR, WHR and BMI with the heterozygous genotype of the TJP1 SNP rs2291166 and the long and short repeats of the ATXN2 CAG repeat in obese adolescent patients. A very strong positive correlation was seen between the TJP1 SNP and the HOMA-IR index (P<.05). A positive correlation was also found between the ATXN2 CAG repeat and the QUICKI index (P=.000) (P<.05), while the DQIs index correlated more closely with BMI and WHR. CONCLUSIONS: DQIs, TJP1 SNP rs2291166, and ATXN2 CAG repeat are determinants of obesity-related risk parameters such as BMI, WHR, QUICKI, and HOMA-IR in the adolescent population analyzed.

Influence of the CYP2J2 Gene Polymorphisms on Chronic Obstructive Pulmonary Disease Risk in the Chinese Han Population.

INTRODUCTION: Cytochrome P450 (CYP) 2J2 is a major enzyme that controls epoxyeicosatrienoic acids biosynthesis, which may play a role in chronic obstructive pulmonary disease (COPD) development. In this study, we aimed to assess the influence of CYP2J2 polymorphisms with COPD susceptibility. MATERIAL AND METHODS: A case-control study enrolled 313 COPD cases and 508 controls was to investigate the association between CYP2J2 polymorphisms and COPD risk. Agena MassARRAY platform was used to genotype CYP2J2 polymorphisms. Odds ratios (OR) and 95% confidence intervals (CI) were calculated to evaluate the association between CYP2J2 polymorphisms and COPD risk. RESULTS: We observed rs11207535 (homozygote: OR=0.08, 95%CI=0.01-0.96, p=0.047; recessive: OR=0.08, 95%CI=0.01-0.94, p=0.044), rs10889159 (homozygote: OR=0.08, 95%CI=0.01-0.92, p=0.043; recessive: OR=0.08, 95%CI=0.01-0.90, p=0.040) and rs1155002 (heterozygote: OR=1.63, 95%CI=1.13-2.36, p=0.009; dominant: OR=1.64, 95%CI=1.15-2.35, p=0.006; additive: OR=1.45, 95%CI=1.09-1.92, p=0.011) were significantly associated with COPD risk. Allelic tests showed T allele of rs2280274 was related to a decreased risk of COPD and T allele of rs1155002 was associated with an increased COPD risk. Stratified analyses indicated the effects of CYP2J2 polymorphisms and COPD risk were dependent on gender and smoking status (p<0.05). Additionally, two haplotypes (Ars11207535Crs10889159Trs1155002 and Ars11207535Crs10889159Crs1155002) significantly decreased COPD risk. CONCLUSION: It suggested CYP2J2 polymorphisms were associated with COPD susceptibility in the Chinese Han population.

Análisis bibliométrico de la investigación en genética y la ruptura de ligamento cruzado anterior en deporte: una revisión / Bibliometric analysis of research in genetic and anterior cruciate ligament rupture in sport: a review / Análise bibliométrica da pesquisa em genética e ruptura do ligamento cruzado anterior no esporte: uma revisão

Resumen: Introducción: El componente genético se ha establecido como un factor de riesgo considerable para la ruptura del ligamento cruzado anterior (RLCA). La investigación actual se ha centrado en conocer los genes candidatos que pueden influir y predisponer a un sujeto a padecer esta lesión. Objetivo: Se llevó a cabo un análisis bibliométrico para rastrear los resultados de la indagación e identificar las tendencias globales, así como las brechas en el conocimiento sobre la relación entre el componente genético y la RLCA. Metodología: Los datos fueron extraídos de las bases Pubmed y Scopus, igual que analizados en el paquete Bibliometrix del software R. Se identificó un total de 63 estudios publicados a partir del 2007. Resultados: La mayoría de las publicaciones identificadas fueron artículos de investigación (85.71 %). Los autores con mayor número de aquellas se encuentran en Polonia y Sudáfrica. El análisis a través del mapa de coocurrencias reveló que hay una línea principal de investigación basada en el estudio de polimorfismos genéticos, especialmente en los genes de las familias del colágeno (COL1A1, COL5A1, COL12A1, en mayor frecuencia). Un total de 54 genes candidatos fueron identificados en los estudios. Conclusión: Esperamos que este estudio pueda contribuir a encontrar puntos claves y vacíos de investigación, al proporcionar análisis integrales e información estructurada sobre este tema.

Abstract: Introduction: Genetic component has been established as a significant risk factor for anterior cruciate ligament rupture (ACLR). Current research has focused on knowing the candidate genes that can influence and predispose a subject to this injury. Objective: A bibliometric analysis was carried out to trace the results of the research and identify global trends and gaps in knowledge about the relationship between the genetic component and ACLR. Methodology: Data were extracted from the Pubmed and Scopus databases and analyzed in the Bibliometrix package of the R software. A total of 63 studies published since 2007 were identified. Results: Most of the publications recovered were research articles (85.71%). The authors with the highest number of those are in Poland and South Africa. The analysis through the co-occurrence map reveals that there is a mainline of research based on the study of genetic polymorphisms, especially in the genes of the collagen families (COL1A1, COL5A1, COL12A1, in greater frequency). A total of 54 candidate genes were identified within the studies. Conclusion: We hope that this study can help to find key points and research gaps by providing a comprehensive analysis and structured information on this topic.

Resumo: Introdução: O componente genético foi estabelecido como um fator de risco significativo para a ruptura do ligamento cruzado anterior (RLCA). As pesquisas atuais têm se concentrado em identificar os genes candidatos que podem influenciar e predispor um indivíduo a essa lesão. Objetivo: Foi realizada uma análise bibliométrica para rastrear os resultados das pesquisas e identificar tendências globais e lacunas no conhecimento sobre a relação entre o componente genético e a RLCA. Metodologia: Os dados foram extraídos das bases de dados Pubmed e Scopus e analisados no pacote Bibliometrix do software R. Um total de 63 estudos publicados desde 2007 foram identificados. Resultados: A maioria das publicações recuperadas foram artigos de pesquisa (85,71%). Os autores com o maior número dessas publicações estão na Polônia e na África do Sul. A análise por meio do mapa de coocorrência revela que há uma linha principal de pesquisa baseada no estudo de polimorfismos genéticos, especialmente nos genes das famílias de colágeno (COL1A1, COL5A1, COL12A1, com maior frequência). Um total de 54 genes candidatos foram identificados nos estudos. Conclusão: Esperamos que este estudo possa ajudar a encontrar pontos-chave e lacunas de pesquisa, fornecendo uma análise abrangente e informações estruturadas sobre este tema.

Genetic predisposition of BDNF (rs6265) gene is susceptible to Schizophrenia: A prospective study and updated meta-analysis / Asociación entre el gen BDNF (rs6265) y predisposición a la esquizofrenia: estudio prospectivo y metaanálisis actualizado

Introduction: Genetic polymorphism in the BDNF gene has been found to cause neuronal alterations and has been identified as a causal factor for many neuropsychiatric disorders. Therefore, various neurological case–control studies and meta-analyses have been conducted to find the possible link between BDNF and susceptibility to schizophrenia. Method: This meta-analysis gathered data from 25 case–control studies including a total of 8384 patients with schizophrenia and 8821 controls in order to identify the relationship between the rs6265 single nucleotide polymorphism and the disease, evaluating the combined odds ratio and 95% confidence intervals under 5 different genetic models. Validation followed the “Leave one out” method, and we used the Egger test and Begg's funnel plot to identify publication bias. Results: Research into the rs6265 (G/A) polymorphism revealed a non-significant association with schizophrenia in all 5 genetic models; in the subgroup analysis, no association was found between white and Asian populations, with a p value > .05. Conclusions: Overall, the updated meta-analysis revealed that rs6265 exonic polymorphisms do not increase susceptibility to this disease. However, to better understand the pathogenesis of the disease, there is a need for further case–control studies into the BDNF polymorphism including larger sample sizes and different ethnic groups.(AU)

Introducción: Se sabe que los polimorfismos del gen BDNF provocan alteraciones neuronales y parecen ser un factor causal en muchos trastornos neuropsiquiátricos. Es por ello que se han llevado a cabo varios metaanálisis y estudios de casos y controles con el objetivo de evaluar la posible relación entre BDNF y la esquizofrenia. Método: Realizamos un metaanálisis de 25 estudios de casos y controles, que incluyó un total de 8.384 pacientes con esquizofrenia y 8.821 controles. Se analizó la relación entre el polimorfismo de nucleótido simple rs6265 y la esquizofrenia mediante odds ratios combinados y sus intervalos de confianza del 95% con 5 modelos genéticos diferentes. Utilizamos el método de validación cruzada dejando uno fuera («leave one out»), la prueba de Egger y el gráfico en embudo de Begg para identificar posibles sesgos de publicación. Resultados: Los estudios sobre el polimorfismo rs6265 (G/A) muestran una asociación no significativa con la esquizofrenia en los 5 modelos genéticos. En el análisis por subgrupos, no se encontró relación con las poblaciones caucásica y asiática (p > 0,05). Conclusiones: La presencia de polimorfismos rs6265 no aumenta la predisposición a desarrollar esquizofrenia. Sin embargo, se deben realizar más estudios de casos y controles sobre polimorfismos de BDNF, con muestras más numerosas y con individuos de diferentes grupos étnicos, para comprender mejor los mecanismos patogénicos de la enfermedad.(AU)

Trp64Arg polymorphism of the ADRB3 gene associated with maximal fat oxidation and LDL-C levels in non-obese adolescents.

OBJECTIVE: To analyze the association between the Trp64Arg polymorphism of the ADRB3 gene, maximal fat oxidation rates and the lipid profile levels in non-obese adolescents. METHODS: 72 schoolchildren, of both genders, aged between 11 and 17 years, participated in the study. The anthropometric and body composition variables, in addition to total cholesterol, HDL-c, LDL-c, triglycerides, insulin, and basal glycemia, were evaluated. The sample was divided into two groups according to the presence or absence of the polymorphism: non-carriers of the Arg64 allele, i.e., homozygous (Trp64Trp: n=54), and carriers of the Arg64 allele (Trp64Arg+Arg64Arg: n=18), in which the frequency of the Arg64 allele was 15.2%. The maximal oxygen uptake and peak of oxygen uptake during exercise were obtained through the symptom-limited, submaximal treadmill test. Maximal fat oxidation was determined according to the ventilatory ratio proposed in Lusk's table. RESULTS: Adolescents carrying the less frequent allele (Trp64Arg and Arg64Arg) had higher LDL-c levels (p=0.031) and lower maximal fat oxidation rates (p=0.038) when compared with non-carriers (Trp64Trp). CONCLUSIONS: Although the physiological processes related to lipolysis and lipid metabolism are complex, the presence of the Arg 64 allele was associated with lower rates of FATMAX during aerobic exercise, as well as with higher levels of LDL-c in adolescents.

Analysis of the relationship between interleukin polymorphisms within miRNA-binding regions and alcoholic liver disease. / Análisis de la relación entre polimorfismos en regiones diana de micro-ARN y la enfermedad hepática alcohólica.

INTRODUCTION: Alcohol consumption promotes inflammation through the Toll-like receptor 4 (TLR4)/nuclear factor (NF)-?B pathway, leading to organic damage. Some micro-RNA (miRNA) molecules modulate this inflammatory response by downregulating TLR4/NF-?B pathway mediators, like interleukins (ILs). Thus, polymorphisms within IL genes located near miRNA binding sites could modify the risk of ethanol-induced damage. The present study analyzed potential relationships between alcoholism or alcoholic liver disease (ALD) and IL12B 2124 G>T (rs1368439), IL16 5000 C>T (rs1131445), IL1R1 3114 C>T (rs3917328), and NFKB1 3400 A>G (rs4648143) polymorphisms. PATIENTS AND METHODS: The study included 301 male alcoholic patients and 156 male healthy volunteers. Polymorphisms were genotyped using TaqMan® PCR assays for allelic discrimination. Allele and genotype frequencies were compared between groups. Logistic regression analysis was performed to analyze the inheritance model. RESULTS: Analysis of the IL1R1 (rs3917328) polymorphism showed that the proportion of alleleT carriers (CT and TT genotypes) was higher in healthy controls (9.7%) than in alcoholic patients (6.5%; P=.042). However, multivariable logistic regression analyses did not yield a significant result. No differences between groups were found for other analyzed polymorphisms. CONCLUSIONS: Our study describes, for the first time, the expected frequencies of certain polymorphisms within miRNA-binding sites in alcoholic patients with and without ALD. Further studies should be developed to clarify the potential relevance of these polymorphisms in alcoholism and ALD development.

Associations among SNPs in two addictive genes, food addiction, and antioxidant markers in recreationally active young women / Asociaciones entre polimorfismo de nucleótido único en dos genes adictivos, adicción a la comida y marcadores antioxidantes en mujeres jóvenes recreativamente activas

Introduction: food addiction is associated with genetic polymorphisms and decreased antioxidant intake. Objectives: this study determined the associations among food addiction, dopamine receptor 2 (DRD2) and toll-interleukin 1 receptor (TIR) domain-containing adaptor protein (TIRAP rs625413) gene polymorphisms, antioxidant capacities, and zinc levels among recreationally active Turkish women. Methods: the Yale Food Addiction Scale was used to evaluate the food addiction status. Serum antioxidant capacities and zinc levels were evaluated by blood analyses. Deoxyribonucleic acid (DNA) extraction was performed using peripheral blood leukocytes, and the polymorphism status of the DRD2 Taq 1A and TIRAP genes was investigated using a commercial kit. Results: the frequencies of the heterozygous genotypes of DRD2 Taq 1A and TIRAP were 23.1 % and 31.4 %, respectively, and the frequency of risk allele homozygous genotypes was 3.2 %. Most participants (94.4 %) had a nonpolymorphic/wild (CC) genotype in both genes; however, 11.5 % of the participants had a food addiction. The differences between serum antioxidant capacities, zinc levels, and body mass indices of those with and without food addiction were statistically significant. However, there were no differences in the serum zinc and antioxidant levels among the different genotypes. Conclusion: food addiction in young Turkish women was not associated with DRD2 Taq 1A or TIRAP polymorphisms but was associated with serum antioxidant capacities and zinc levels. Further studies on different loci of the same genes or genotypes of different genes with larger sample sizes are warranted.

Introducción: la adicción a la comida está asociada con polimorfismos genéticos y disminución de la ingesta de antioxidantes. Objetivos: este estudio determinó las asociaciones entre la adicción a la comida, los polimorfismos del gen de la proteína adaptadora que contiene el dominio del receptor de dopamina 2 (DRD2) y del receptor de interleucina 1 (TIR) (TIRAP rs625413), las capacidades antioxidantes y los niveles de zinc entre mujeres turcas recreativamente activas. Métodos: se utilizó la escala de adicción a la comida de Yale para evaluar el estado de adicción a la comida. Las capacidades antioxidantes séricas y los niveles de zinc se evaluaron mediante análisis de sangre. La extracción de ácido desoxirribonucleico (ADN) se realizó a partir de leucocitos de sangre periférica y el estado de polimorfismo de los genes DRD2 Taq 1A y TIRAP se investigó con un kit comercial. Resultados: las frecuencias de los genotipos heterocigotos de DRD2 Taq 1A y TIRAP fueron 23,1 % y 31,4 %, respectivamente, y la frecuencia de genotipos homocigotos de alelos de riesgo fue de 3,2 %. La mayoría de las participantes (94,4 %) tenían un genotipo no polimórfico/salvaje (CC) en ambos genes; sin embargo, el 11,5 % de las participantes tenía adicción a la comida. Las diferencias entre las capacidades antioxidantes séricas, los niveles de zinc y los índices de masa corporal de aquellas con y sin adicción a la comida fueron estadísticamente significativas. Sin embargo, no hubo diferencias en los niveles séricos de zinc y antioxidantes entre los diferentes genotipos. Conclusión: la adicción a la comida en mujeres jóvenes turcas no se asoció con los polimorfismos DRD2 Taq 1A o TIRAP, pero se asoció con las capacidades séricas antioxidantes y los niveles de zinc. Se justifican más estudios sobre diferentes loci de los mismos genes o genotipos de diferentes genes con tamaños de muestra más grandes. (AU)

Factores de riesgo de deterioro cognitivo asociado a cáncer en pacientes con carcinoma de mama y colon que reciben tratamiento con quimioterapia / Risk factors for cancer-related cognitive impairment in breast and colorectal cancer patients who undergo chemotherapy

Fundamento: Nuestro estudio se plantea con el objetivo deevaluar el impacto de diferentes factores individuales sobre eldeterioro cognitivo relacionado con el cáncer en pacientes tratados con quimioterapia. Material y métodos: Estudio unicéntrico longitudinal prospectivo. Incluyó pacientes con carcinoma de mama y colon tratados con quimioterapia. Se recogieron variables clínicas y genéticas del paciente (polimorfismos de nucleótido simple, SNP). Los pacientes fueron evaluados neurocognitivamente con oncetest validados, en tres momentos: basal previo a quimioterapia(M0), entre una y cuatro semanas tras finalizar quimioterapia(M1) y entre 24-30 semanas tras finalizar quimioterapia (M2). Resultados: Se incluyeron 62 pacientes, 82% mujeres, con mediana de edad de 56 años (rango 30-74), un 64,5% con cáncer demama. La edad <55 años, tener estudios superiores, ausenciade comorbilidades y presencia de la variante CC de rs471692(TOP2A) se asociaron, en general, con mejores resultados cognitivos en M0. Se observó un empeoramiento significativo deM0 a M1 en los test RAVLT y Letras y números, y recuperaciónen M2 respecto a M0 en los test de memoria visual, FAST, clavede números, y cubos. La edad ≥55 años, la quimioterapia adyuvante, las comorbilidades, el consumo de tabaco y de alcoholy la variante GT de rs1800795 se relacionaron con el deterioroentre M0 y M1 en el modelo multivariante. Conclusiones: La edad mayor de 55 años, el sexo femenino, lapresencia de comorbilidades y el nivel básico de estudios serelacionan con un mayor riesgo de deterioro cognitivo tras eltratamiento con quimioterapia.(AU)

Background: Our study aims to evaluate the impact of differentfactors on cancer-related cognitive impairment in patients whoundergo chemotherapy.Methodology: Prospective longitudinal single-centre studythat included patients with breast and colon carcinoma whounderwent chemotherapy as part of their treatment. Clinicaland genetic characteristics of the patients (single nucleotidepolymorphisms, SNPs) were collected. Patients’ neurocognitivestatus was assessed using eleven validated tests at three timepoints: before chemotherapy (M0 - baseline), between one andfour weeks after completing chemotherapy (M1), and between24-30 weeks after completing chemotherapy (M2).Results: Sixty-two patients were included in this study; 82% werefemale, median age was 56 years (range 30-74), and 64.5% had beendiagnosed with breast cancer. Overall, better cognitive results atM0 were associated with age < 55 years, higher educational level,absence of comorbidities, and the CC variant rs471692 (TOP2A).Significant decline was found between M0 to M1 in the Rey Auditory Verbal Learning Test and the Letter and Number test, with evidence of recovery in M2 compared to M0 regarding the followingtest: Visual Memory, Functioning Assessment Short Test (FAST),Digit Symbol Substitution and Cube. In the multivariate analysis,being ≥55 years of age, adjuvant chemotherapy, presence of comorbidities, tobacco and alcohol use, and GT variant rs1800795were associated with cognitive decline between M0 and M1.Conclusion: Being ≥55 years of age, female, presence of comorbidities and basic education level are related to a higher risk ofcognitive impairment after chemotherapy.(AU)

Genetic Polymorphisms in COL1A2 gene and the Risk of Tendinopathy: Case-Control Study / Polimorfismos genéticos no gene COL1A2 eo risco de tendinopatia: Estudo de caso-controle

Abstract Objective To evaluate the influence of polymorphisms on genes encoding type I collagen and the genetic susceptibility of tendinopathy. Methodology Case-control study involving 242 Brazilian athletes from different sports modalities (55 cases of tendinopathy and 187 controls). The polymorphisms COLIAI (rs1107946) and COLIA2 (rs412777, rs42524, and rs2621215) were analyzed by theTaqMansystem. Odds ratio(OR)withtheir 95% confidence intervals (CIs) were calculated using a nonconditional logistic regression model. Results The mean age was 24.0 ± 5.6 years old and 65.3% were men. Of the 55 cases of tendinopathy, 25.4% had > 1 affected tendon, the most frequent being patellar (56.3%), rotator cuff (30.9%) and elbow or hand flexors (30.9%). Age and amount of time of sports practice were associated with a higher chance of presenting tendinopathy (5 and 8 times, respectively). The frequency of variant alleles in control and case patients, respectively, was: COLIAI rs1107946 24.0 and 29.6%; COLIA2 rs412777 36.1 and 27.8%; rs42524 17.5 and 25.9%; and rs2621215 21.3 and 27.8%. After adjusting for confounding factors (age and years of sports practice), COLIA2 rs42524and rs2621215 polymorphisms were associated with increased risk of tendinopathy (OR = 5.5; 95% CI = 1.2-24.6 and OR = 3.9; IC95% = 1.1-13.5, respectively). The haplotype COLIA2 CGT was associated with low risk for disease development (OR = 0.5; 95%CI = 0.3-0.9). Conclusion Age (≥ 25 years old), time of sports practice (≥ 6years) and polymorphisms in the COLIA2 gene increased the risk of developing tendinopathy.

Resumo Objetivo Avaliar a influência de polimorfismos nos genes que codificam o colágeno tipo I e a suscetibilidade genética da tendinopatia. Metodologia Estudo caso-controle envolvendo 242 atletas brasileiros de diferentes modalidades esportivas (55 casos de tendinopatia e 187 controles). Os polimorfismos COL1A1 (rs1107946) e COL1A2 (rs412777, rs42524 e rs2621215) foram analisados pelo sistema TaqMan. As razões de chance (OR) com seus intervalos de confiança (IC) de 95% foram calculadas usando um modelo de regressão logística não-condicional. Resultados A média de idade foi de 24,0 ± 5,6 anos e 65,3% eram homens. Dos 55 casos de tendinopatia, 25,4% apresentaram mais de um tendão acometido, sendo os maisfrequentesopatelar(56,3%),omanguitorotador(30,9%)eodocotoveloou flexores das mãos (30,9%). A idade e o tempo de prática esportiva foram associados a uma maior chance de apresentar tendinopatia (5 e 8 vezes, respectivamente). A frequência dos alelos variantes nos controles e casos, respectivamente, foi: COL1A1 rs1107946 24,0 e 29,6%; COL1A2 rs412777 36,1 e 27,8%; rs42524 17,5 e 25,9%; e rs2621215 21,3 e 27,8%. Após ajuste pelos fatores de confundimento (idade e anos de práticas esportiva), os polimorfismos COL1A2 rs42524 e rs2621215 foram associados a um risco aumentado de tendinopatia (OR = 5,5; IC95% = 1,2-24,6 e OR = 3,9; IC95% = 1,1-13,5, respectivamente). O haplótipo COL1A2 CGT foi associado a um baixo risco para desenvolvimento da doença (OR = 0,5; IC95% = 0,3-0,9). Conclusão Aidade (> 25 anos), o tempo de prática esportiva (> 6 anos) e polimorfismos no gene COL1A2 aumentaram o risco de desenvolvimento da tendino-patia.

Polimorfismos genéticos implicados en el desarrollo de la purpura trombocitopénica inmune / Genetic polymorphisms involved in the development of Immune Thrombocytopenic Purpura

Introducción: los cambios en el ácido desoxirribonucleico se conocen como mutaciones, estas dan lugar a los polimorfismos, los cuales generan variación alélica entre individuos y diversidad de la misma especie. Se ha sugerido que los polimorfismos genéticos en los mediadores inmunitarios desempeñan un papel fundamental en la patogénesis de muchos trastornos autoinmunes, como en la púrpura trombocitopénica inmune, siendo esta el tipo más común de púrpura trombocitopénica y, a menudo, se diagnostica como un tipo de trastorno autoinmune, debido a la destrucción de las plaquetas mediadas por el sistema inmunitario. Objetivo: realizar una revisión bibliográfica sobre el papel de los polimorfismos genéticos y su influencia en el desarrollo de la púrpura trombocitopénica inmune. Métodos: se realizó revisión literaria en inglés y español en PubMed y Elsevier, desde marzo hasta mayo del 2021, con el uso de combinación de palabras clave y términos MeSH, como púrpura trombocitopénica y polimorfismos genéticos. Se realizó análisis y resumen de la literatura encontrada. Conclusión: la púrpura trombocitopénica inmune es considerada como una patología multifactorial, causada por factores ambientales y genéticos, dentro de los cuales se encuentran los polimorfismos para los mediadores inmunitarios que pueden llevar a una exacerbación de la enfermedad o no intervenir en la misma.

Introduction: Changes in deoxyribonucleic acid are known as mutations, these give place to polymorphisms, which generate allelic variation between individuals and provide diversity among same species. Genetic polymorphisms in immune mediators have been suggested to play a key role in the pathogenesis of many autoimmune disorders, such as immune thrombocytopenic purpura, this being the most common type of thrombocytopenic purpura and is often diagnosed as a type of autoimmune disorder, due to the destruction of platelets mediated by the immune system. Objective: To execute a bibliographic review on the role of genetic polymorphisms and their influence on the development of immune thrombocytopenic purpura. Methods: A literary review in English and Spanish was performed in PubMed and Elsevier from March to May 2021, with the use of a combination of keywords and MeSH terms such as Thrombocytopenic Purpura and genetic polymorphisms. Analysis and summary of the literature found was executed. Conclusion: Immune thrombocytopenic purpura is considered a multifactorial pathology, caused by environmental and genetic factors, among which are polymorphisms for immune mediators that can lead to an exacerbation of the disease or not intervene in the same.

Polimorfismo (cag) del gen atxn2 como factor de riesgo relacionado con diabetes mellitus tipo 2 / Polymorphism (cag) of the atxn2 gene as a risk factor related to type 2 diabetes mellitus / Polimorfismo (cag) do gene atxn2 como fator de risco relacionado ao diabetes mellitus tipo 2

La diabetes mellitus tipo 2 (DM2) es una de las patologías con más prevalencia a nivel mundial, se estima que alrededor de 425 millones de habitantes viven actualmente con DM2 según la OMS, la importancia de realizar pruebas moleculares que permitan realizar un diagnóstico temprano conlleva el análisis de varios grupos de genes implicados en el fenotipo diabético con una marcada resistencia a la insulina y en la mayoría de los casos obesidad, entre los cuales están el polimorfismo de CAG(n) en el ATXN2 gen encontrado en el cromosoma 12q24. Objetivo. Conocer el estado actual del gen ATXN2 en relación al número variable de repeticiones en tándem (VNTR) del trinucleótido CAG(n) y su posible asociación con el desarrollo de la diabetes mellitus tipo 2. Metodología. Se llevó a cabo una revisión sistemática mediante la búsqueda de información en las bases de datos de PubMed, Google Scholar y Elsevier. Para ello, se combinaron palabras clave relevantes, como "diabetes mellitus tipo 2", "polimorfismo CAG" y "ATXN2 gen", junto con "Epigenética de la DM2". Se seleccionaron artículos originales y estudios experimentales publicados en revistas de alto impacto utilizando Scimago Journal Ranks para garantizar la calidad de la literatura revisada. Conclusión. Se determinó la relación entre el ATXN2 y el VNTR CAG(n) y la actividad transcripcional del gen en la DM2 y otras patologías neurodegenerativas es evidente. Sin embargo, para profundizar en este tema, es necesario ampliar el campo de estudio en Ecuador y en otros países latinoamericanos, a fin de analizar la variabilidad genética y su posible relación con la DM2 en esta población.

Diabetes mellitus type 2 (DM2) is one of the most prevalent pathologies worldwide, it is estimated that about 425 million inhabitants currently live with DM2 according to WHO, the importance of molecular tests that allow early diagnosis involves the analysis of several groups of genes involved in the diabetic phenotype with marked insulin resistance and in most cases obesity, among which are the CAG(n) polymorphism in the ATXN2 gene found on chromosome 12q24. Objective. To know the current status of the ATXN2 gene in relation to the variable number of tandem repeats (VNTR) of the CAG(n) trinucleotide and its possible association with the development of type 2 diabetes mellitus. Methodology. A systematic review was carried out by searching for information in PubMed, Google Scholar and Elsevier databases. For this purpose, relevant keywords, such as "type 2 diabetes mellitus", "CAG polymorphism" and "ATXN2 gene" were combined with "Epigenetics of DM2". Original articles and experimental studies published in high impact journals were selected using Scimago Journal Ranks to ensure the quality of the reviewed literature. Conclusion. The relationship between ATXN2 and VNTR CAG(n) was determined and the transcriptional activity of the gene in DM2 and other neurodegenerative pathologies is evident. However, in order to go deeper into this topic, it is necessary to expand the field of study in Ecuador and in other Latin American countries, in order to analyze the genetic variability and its possible relationship with DM2 in this population.

La diabetes mellitus tipo 2 (DM2) es una de las patologías con más prevalencia a nivel mundial, se estima que alrededor de 425 millones de habitantes viven actualmente con DM2 según la OMS, la importancia de realizar pruebas moleculares que permitan realizar un diagnóstico temprano conlleva el análisis de varios grupos de genes implicados en el fenotipo diabético con una marcada resistencia a la insulina y en la mayoría de los casos obesidad, entre los cuales están el polimorfismo de CAG(n) en el ATXN2 gen encontrado en el cromosoma 12q24. Objetivo. Conocer el estado actual del gen ATXN2 en relación al número variable de repeticiones en tándem (VNTR) del trinucleótido CAG(n) y su posible asociación con el desarrollo de la diabetes mellitus tipo 2. Metodología. Se llevó a cabo una revisión sistemática mediante la búsqueda de información en las bases de datos de PubMed, Google Scholar y Elsevier. Para ello, se combinaron palabras clave relevantes, como "diabetes mellitus tipo 2", "polimorfismo CAG" y "ATXN2 gen", junto con "Epigenética de la DM2". Se seleccionaron artículos originales y estudios experimentales publicados en revistas de alto impacto utilizando Scimago Journal Ranks para garantizar la calidad de la literatura revisada. Conclusión. Se determinó la relación entre el ATXN2 y el VNTR CAG(n) y la actividad transcripcional del gen en la DM2 y otras patologías neurodegenerativas es evidente. Sin embargo, para profundizar en este tema, es necesario ampliar el campo de estudio en Ecuador y en otros países latinoamericanos, a fin de analizar la variabilidad genética y su posible relación con la DM2 en esta población.

The role of IL10 and IL17 gene polymorphisms in treatment response in children and adolescents with severe asthma / O papel de polimorfismos dos genes IL10 e IL17 na resposta ao tratamento em crianças e adolescentes com asma grave

ABSTRACT Objective: To determine whether polymorphisms of the IL10 and IL17 genes are associated with severe asthma control and bronchodilator reversibility in children and adolescents with severe asthma. Methods: This was a cross-sectional study, nested within a prospective cohort study of patients with severe asthma. Two outcomes were evaluated: asthma control and bronchodilator reversibility. We extracted DNA from peripheral blood and genotyped three single nucleotide polymorphisms: rs3819024 and rs2275913 in the IL17A gene; and rs3024498 in the IL10 gene. For the association analyses, we performed logistic regression in three genetic models (allelic, additive, and dominant). Results: The rs3024498 C allele in the IL10 gene was associated with failure to achieve asthma control despite regular treatment (p = 0.02). However, the G allele of the IL17A rs3819024 polymorphism was associated with failure to respond to stimulation with a b2 agonist. The rs2275913 polymorphism of the IL17A gene showed no relationship with asthma control or bronchodilator reversibility. Conclusions: In pediatric patients with severe asthma, the IL10 polymorphism appears to be associated with failure to achieve clinical control, whereas the IL17A polymorphism appears to be associated with a worse bronchodilator response. Knowledge of the involvement of these polymorphisms opens future directions for pharmacogenetic studies and for the implementation of individualized therapeutic management of severe asthma in pediatric patients.

RESUMO Objetivo: Determinar se existe relação entre polimorfismos dos genes IL10 e IL17 e controle da asma grave e reversibilidade com broncodilatador em crianças e adolescentes com asma grave. Métodos: Estudo transversal, aninhado em um estudo prospectivo de coorte com pacientes com asma grave. Foram avaliados dois desfechos: controle da asma e reversibilidade com broncodilatador. Extraímos DNA do sangue periférico e genotipamos três polimorfismos de nucleotídeo único: rs3819024 e rs2275913 no gene IL17A e rs3024498 no gene IL10. Para as análises de associação, realizamos regressão logística em três modelos genéticos (alélico, aditivo e dominante). Resultados: O alelo C do polimorfismo rs3024498 do gene IL10 apresentou relação com asma que permaneceu descontrolada mesmo com tratamento regular (p = 0,02). No entanto, o alelo G do polimorfismo rs3819024 do gene IL17A apresentou relação com ausência de resposta ao estímulo com b2-agonista. O polimorfismo rs2275913 do gene IL17A não apresentou relação com controle da asma ou reversibilidade com broncodilatador. Conclusões: Em pacientes pediátricos com asma grave, o polimorfismo do gene IL10 parece estar relacionado com ausência de controle clínico, ao passo que o polimorfismo do gene IL17A parece estar relacionado com pior resposta ao broncodilatador. O conhecimento a respeito do envolvimento desses polimorfismos abre perspectivas futuras para estudos farmacogenéticos e para a implantação de manejo terapêutico individualizado da asma grave em pacientes pediátricos.

Estudios genéticos del metabolismo de la warfarina y su utilidad en la toma de decisiones / Genetic studies of warfarin metabolism and its usefulness in decision making

Resumen Introducción: Al momento de valorar la necesidad de realizar un reemplazo quirúrgico valvular cardiaco es posible elegir entre una válvula mecánica o una bioprotésica; la elección debe tener presentes los riesgos de la terapia anticoagulante y la necesidad potencial o el riesgo de nuevas intervenciones. La anticoagulación se realiza con antagonistas de la vitamina K, y de estos, la warfarina es el que se prescribe con mayor frecuencia. Por su metabolismo hepático (P450), dicho medicamento tiene múltiples interacciones farmacológicas y no farmacológicas que en ocasiones se convierten en un verdadero problema en la práctica clínica. Hasta la fecha no se recomienda realizar de forma rutinaria una dosificación guiada por genotipo; sin embargo, se requieren estudios genéticos para definir conductas médicas cuando se hace difícil su manejo. Caso clínico: Se describe el caso de una mujer de 37 años portadora de una válvula mitral mecánica por enfermedad reumática, anticoagulada de forma crónica con warfarina; sin embargo, durante el seguimiento tuvo múltiples consultas a urgencias (entre dos y tres veces por mes) por niveles de anticoagulación en rangos subterapéuticos, como valores elevados de INR. Presentó infarto agudo de miocardio con coronarias sanas e isquemia cerebral transitoria en contexto de INR bajo, considerados así de etiología tromboembólica. Por estas dificultades se decidió realizar la medición de los niveles de factor II de la coagulación, el cual fue normal a pesar del uso del medicamento, por lo que se sospechó resistencia al fármaco. Se solicitó estudio genético que mostró genotipo asociado con actividad enzimática reducida o normal de la CYP2C9, además un genotipo WARF CYP2C9 *1/*2 y WARF VKORC1 A/A, con lo cual se concluyó que la paciente presentaba un comportamiento metabólico divergente para warfarina. Se decidió realizar un reemplazo de válvula mecánica por válvula bioprotésica, con el objetivo de suspender el uso de la warfarina. La paciente presentó una evolución clínica satisfactoria. Conclusiones: La farmacogenética ha logrado identificar polimorfismos en los genes implicados en el metabolismo de la warfarina, los cuales están relacionados con riesgo de sangrado. Estas variantes se encuentran relacionadas con los genes CYP2C9, CYP4F2 y VKORC1. Si bien no se ha demostrado un impacto clínico en los ajustes de warfarina guiados por genotipo, dichos exámenes se hacen necesarios en algunos casos para sugerir un cambio en la dosis del medicamento o su suspensión definitiva.

Abstract Introduction: When assessing the need for a cardiac valvular surgical replacement, it is possible to choose between a mechanical or bioprosthetic valve; The choice must take into account the risks of anticoagulant therapy and the potential need and/or risk of new interventions. Anticoagulation is performed with vitamin K antagonists and warfarin is the most commonly prescribed of these. This medicine due to its hepatic metabolism (P450) has multiple pharmacological and non-pharmacological interactions that sometimes become a real problem in clinical practice. To date, it is not recommended to routinely perform a genotype-guided dosage. However, such genetic studies are necessary to define medical behaviors when handling is difficult. Case report: It is described a case of a 37-year-old woman with a mechanical mitral valve due to rheumatic disease, chronically anticoagulated with warfarin; however, during the follow-up with multiple emergency consultations (2-3 times per month) for anticoagulation levels in subtherapeutic ranges such as elevated INR levels. She presented acute myocardial infarction with healthy coronary arteries and transient cerebral ischemia in the context of low INR thus considered thromboembolic etiology. Due to these difficulties, it was decided to measure coagulation factor II levels, which was normal despite the use of the drug, suspecting drug resistance. A genetic study was requested that showed genotype associated with reduced or normal CYP2C9 enzymatic activity, plus a WARF CYP2C9 * 1/* 2 and WARF VKORC1 A/A genotype concluding that the patient presented a divergent metabolic behavior for warfarin. It was decided to perform a mechanical valve replacement with a bioprosthetic valve, in order to suspend the use of warfarin. The patient presented a satisfactory clinical evolution. Conclusions: Pharmacogenetics has managed to identify polymorphisms in the genes involved in warfarin metabolism, which are related to bleeding risk. These variants are related to the CYP2C9, CYP4F2 and VKORC1 genes. Although no clinical impact has been demonstrated in genotype-guided warfarin adjustments, such tests are necessary in some cases to suggest a change in the dose of the medication or the definitive suspension.

Associação do polimorfismo genético da Cromogranina A com pacientes portadores de câncer de tireoide / Association of chrogranin A (CHGA) genetic polymorphism with patients with thyroid câncer / Asociación del polimorfismo genético de la crogranina A (CHGA) con pacientes con cáncer de tiroides

Objetivo: Descrever a presença do polimorfismo da região codante do gene CHGA Glu264Asp e associa-lo com as características clinicas da doença. Método: Trata-se de um estudo transversal, descritivo e de caso controle para investigar o polimorfismo da CHGA Glu264Asp por meio de amostras de sangue de 53 indivíduos sendo o grupo caso, formado por 23 pacientes, de ambos os sexos, que sofreram a tireoidectomia e foram submetidos ao tratamento com o Radiofármaco Iodeto de Sódio (I131). Para a genotipagem foi utilizada a técnica PCRRFLP. Foi adotado o nível de significância de 5%. Resultados: Houve diferença estatística significativa na distribuição alélica entre indivíduos com câncer papilífero da tireoide e os sadios. Com tudo, a presença do alelo G é um fator de risco para o câncer papilífero da tireoide. Observou-se uma correlação entre o genótipo GG com o aumento do nível de TSH em pacientes que apresentavam essa patologia. Conclusão: Demostrou-se que o alelo selvagem pode ser um fator de risco para o desenvolvimento da neoplasia tireoidiana do tipo papilar. Por ser uma doença de etiologia multifatorial, são necessários outros estudos em populações diferentes para melhor compreensão da doença.

Objective: To describe the presence of polymorphism of the codante region of the CHGA Glu264Asp gene and to associate it with the clinical characteristics of the disease. Method: This is a cross-sectional, descriptive and case-control study to investigate chga glu264Asp polymorphism through blood samples from 53 individuals, consisting of 23 patients of both sexes who underwent thyroidectomy and underwent treatment with the Radiopharmaceutical Sodium Iodide (I131). Pcr-RFLP technique was used for genotyping. The significance level of 5% was adopted. Results: There was a statistically significant difference in the allelic distribution between individuals with papillary thyroid cancer and healthy individuals. With everything, the presence of the G alllet is a risk factor for papillary thyroid cancer. A correlation was observed between the GG genotype and the increased level of TSH in patients with this pathology. Conclusion: It was shown that the wild allomay be a risk factor for the development of the thyroid neoplasm of the papilar type. As it is a disease of multifactorial etiology, further studies in different populations are needed to better understand the disease

Objetivo: Describir la presencia de polimorfismo de la región codante del gen CHGA Glu264Asp y asociarlo con las características clínicas de la enfermedad. Método: Estudio transversal, descriptivo y de casos y controles para investigar el polimorfismo chga glu264Asp a través de muestras de sangre de 53 individuos, constituido por 23 pacientes de ambos sexos sometidos a tiroidectomía y tratamiento con yoduro de sodio radiofarmacéutico (I131). Se utilizó la técnica Pcr-RFLP para el genotipado. Se adoptó el nivel de significancia del 5%. Resultados: Hubo una diferencia estadísticamente significativa en la distribución alélica entre individuos con cáncer papilar de tiroides e individuos sanos. Con todo, la presencia del Gallete G es un factor de riesgo para el cáncer papilar de tiroides. Se observó una correlación entre el genotipo GG y el aumento del nivel de TSH en pacientes con esta patología. Conclusión: Se demostró que el aloplasma silvestre puede ser un factor de riesgo para el desarrollo de la neoplasia tiroidea del tipo papilar. Como es una enfermedad de etiología multifactorial, se necesitan más estudios en diferentes poblaciones para comprender mejor la enfermedad

Papillophlebitis versus paediatric venous thrombosis. A case with 46C/T polymorphism in the F12 coagulation gene. / Papiloflebitis versus trombosis venosa pediátrica. Un caso con polimorfismo C46T del gen F12 de la coagulación.

CLINICAL CASE: An 8 year-old boy with no known diseases, with sudden loss of visual acuity (VA) in the left eye (LE). EXAMINATION: VA 1 in right eye, and 0.1 in LE, discrete left relative afferent pupil defect (RAPD). Normal biomicroscopy. Funduscopy: congestive papilla, venous tortuosity, peripapillary haemorrhages with macular oedema in LE. The systemic study only revealed A C46Tpolymorphism in the F12 coagulation gene. He had a VA of 1 and normal funduscopy 8 months later. DISCUSSION: Papillophlebitis is an inflammatory and non-ischaemic central retinal vein occlusion, ophthalmoscopically similar to central retinal vein thrombosis. The systemic study is essential to rule out underlying diseases.

Analysis of the influence of the T393C polymorphism of the GNAS gene on the clinical expression of primary hyperparathyroidism.

BACKGROUND: The receptor of parathyroid hormone and parathyroid hormone-related-protein (PTH/PTHrp) is located in the cell membrane of target tissues - kidney and osteoblasts. It is a G protein-coupled-receptor whose Gsα subunit is encoded by the GNAS gene. Our aim was to study whether the single nucleotide polymorphism (SNP) T393C of the GNAS gene is associated with renal stones, bone mineral density (BMD), or bone remodelling markers in primary hyperparathyroidism (PHPT). METHODS: An analysis was made of clinical and biochemical parameters and densitometric values in three areas and their relationship with the T393C SNP of the GNAS gene in 261 patients with primary hyperparathyroidism and in 328 healthy controls. Genotyping was performed using the Custom Taqman® SNP Genotyping assay. RESULTS: The genotype frequencies of GNAS T/C 393 were similar in the control and PHPT groups. No association was found between genotypes and clinical expression of PHPT (renal stones and bone fractures). A nonstatistically significant trend was seen to lower BMD in the lumbar spine, femoral neck, and total hip in both PHPT and control C homozygote subjects. CONCLUSION: Genetic susceptibility to PHPT related to the GNAS T393C polymorphism or a major influence in its development and clinical expression were found. A C allele-related susceptibility to lower BMD in trabecular bone in both PHPT and control subjects is not sufficient to suggest a more severe clinical expression of PHPT. This trend may be considered as a basis for further studies with larger sample sizes and complementary functional evaluation.

Evaluation of the g473a polymorphism in the lysyl oxidase gene as a risk factor related to the occurrence of breast cancer in Brazilian women / Avaliação do polimorfismo g473a no gene da lisil oxidase como fator de risco relacionado à ocorrência de câncer de mama em mulheres brasileiras

Introdução: o câncer de mama é o tipo de câncer mais diagnosticado e a principal causa de morte entre as mulheres em todo o mundo. Aproximadamente 1,67 milhões de novos casos de câncer de mama foram diagnosticados em 2012, levando a mais de meio milhão de mortes. O câncer de mama foi responsável por 11,6% dos novos casos de cânceres diagnosticados (2.089 milhões) e 9,2% (787.000) das mortes relacionadas ao câncer para ambos os sexos e em todas as idades em todo o mundo em 2018.Objetivo: o câncer de mama como o carcinoma mais diagnosticado no mundo e a principal causa de morte entre as mulheres, é uma morbidade de grande importância, sendo o objetivo deste estudo avaliar a associação entre o polimorfismo do gene LOX G473A (rs1800449) a ocorrência de câncer de mama, potencialmente estabelecendo um novo achado na identificação de riscos, prevenção, e atendimento a um grupo específico de mulheres.Método: neste estudo de coorte retrospectivo, a frequência do polimorfismo LOX G473A foi avaliada em 148 mulheres com câncer de mama e 245 mulheres sem a doença. Todas as pacientes responderam a um questionário para identificação de possíveis fatores de risco e posteriormente realizaram coleta de sangue periférico para estudo do gene LOX. O DNA foi extraído seguido da amplificação gênica via PCR, e o polimorfismo foi estudado por eletroforese de fragmentos específicos após digestão das amostras com a endonuclease de restrição do organismo Providencia stuartii.Resultados: este estudo identificou o uso de anticoncepcional oral e o antecedente familiar de câncer de mama como fatores de risco par a doença; o polimorfismo G473A na LOX não foi identificado como fator de risco.Conclusão: não foi observada relação entre o polimorfismo LOX G473A e a ocorrência de câncer de mama.

Introduction: breast cancer is the most diagnosed type of cancer and the leading cause of death among women worldwide. Approximately 1.67 million new cases of breast cancer were diagnosed in 2012, leading to more than half a million deaths. Breast cancer accounted for 11.6% of newly diagnosed cancers (2,089 million) and 9.2% (787,000) of cancer-related deaths for both sexes and at all ages worldwide in 2018.Objective: breast cancer, as the most diagnosed carcinoma in the world and the leading cause of death among women, is a morbidity of outstanding importance, and the object of this study is to evaluate the association between the LOX gene G473A (rs1800449) polymorphism and breast cancer occurrence, potentially establishing a new finding in the identification of risks, prevention, and care for a specific group of women.Methods:in this retrospective cohort study, LOX G473A polymorphism frequency was assessed in 148 women with breast cancer and 245 women without breast cancer. All patients completed a questionnaire to identify possible risk factors and subsequently underwent peripheral blood collection to study the LOX gene. DNA was extracted followed by gene amplification via PCR, and the polymorphism was studied by specific fragment electrophoresis after digestion of the samples with the restriction endonuclease Pstl.Results: this study identified the use of oral contraceptives and family history of breast cancer as risk factors for breast cancer; the G473A polymorphism in LOX was not identified as a risk factor.Conclusion: a relationship was not observed between the LOX G473A polymorphism and the occurrence of breast cancer.