Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 125.546
Filtrar
1.
Braz. j. oral sci ; 20: e211654, jan.-dez. 2021. ilus
Artículo en Inglés | LILACS, BBO - Odontología | ID: biblio-1254524

RESUMEN

Grade C periodontitis in youngers is characterized by a severe form of periodontitis, and IL10 rs6667202 single nucleotide polymorphism (SNP) has been described as an important feature in this disease etiology. Aim: This study aimed to evaluate, in vivo, the functionality of IL10 rs6667202 SNP on IL-10 gingival fluid levels. Methods: Thirty patients with Perio4C were selected, 15 with the IL10 AA genotype (rs6667202) and 15 with AC/CC genotypes. The gingival fluid was collected from two sites with probing depth ≥ 7 mm and bleeding on probing, and two healthy sites. The IL-10 concentration was determined by Luminex/MAGpix platform. Results: In deep pockets, the IL10 AA genotype presented a lower concentration of IL-10 when compared with AC or CC genotypes (p<0.05). In shallow pockets, no difference between groups was seen (p>0.05). Conclusion: IL10 rs6667202 SNP decreases the production of IL-10 in crevicular fluid, potentially affecting this disease progression


Asunto(s)
Humanos , Masculino , Femenino , Periodontitis Agresiva , Interleucina-10 , Polimorfismo de Nucleótido Simple
2.
BMC Genomics ; 22(1): 636, 2021 Sep 02.
Artículo en Inglés | MEDLINE | ID: mdl-34474664

RESUMEN

BACKGROUND: Association mapping studies of quantitative trait loci (QTL) for canine hip dysplasia (CHD) can contribute to the understanding of the genetic background of this common and debilitating disease and might contribute to its genetic improvement. The power of association studies for CHD is limited by relatively small sample numbers for CHD records within countries, suggesting potential benefits of joining data across countries. However, this is complicated due to the use of different scoring systems across countries. In this study, we incorporated routinely assessed CHD records and genotype data of German Shepherd dogs from two countries (UK and Sweden) to perform genome-wide association studies (GWAS) within populations using different variations of CHD phenotypes. As phenotypes, dogs were either classified into cases and controls based on the Fédération Cynologique Internationale (FCI) five-level grading of the worst hip or the FCI grade was treated as an ordinal trait. In a subsequent meta-analysis, we added publicly available data from a Finnish population and performed the GWAS across all populations. Genetic associations for the CHD phenotypes were evaluated in a linear mixed model using 62,089 SNPs. RESULTS: Multiple SNPs with genome-wide significant and suggestive associations were detected in single-population GWAS and the meta-analysis. Few of these SNPs overlapped between populations or between single-population GWAS and the meta-analysis, suggesting that many CHD-related QTL are population-specific. More significant or suggestive SNPs were identified when FCI grades were used as phenotypes in comparison to the case-control approach. MED13 (Chr 9) and PLEKHA7 (Chr 21) emerged as novel positional candidate genes associated with hip dysplasia. CONCLUSIONS: Our findings confirm the complex genetic nature of hip dysplasia in dogs, with multiple loci associated with the trait, most of which are population-specific. Routinely assessed CHD information collected across countries provide an opportunity to increase sample sizes and statistical power for association studies. While the lack of standardisation of CHD assessment schemes across countries poses a challenge, we showed that conversion of traits can be utilised to overcome this obstacle.


Asunto(s)
Displasia Pélvica Canina , Animales , Perros , Estudio de Asociación del Genoma Completo , Genotipo , Displasia Pélvica Canina/genética , Fenotipo , Polimorfismo de Nucleótido Simple , Sitios de Carácter Cuantitativo
3.
BMC Bioinformatics ; 22(1): 417, 2021 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-34470617

RESUMEN

BACKGROUND: Variation in mitochondrial DNA (mtDNA) identified by genotyping microarrays or by sequencing only the hypervariable regions of the genome may be insufficient to reliably assign mitochondrial genomes to phylogenetic lineages or haplogroups. This lack of resolution can limit functional and clinical interpretation of a substantial body of existing mtDNA data. To address this limitation, we developed and evaluated a large, curated reference alignment of complete mtDNA sequences as part of a pipeline for imputing missing mtDNA single nucleotide variants (mtSNVs). We call our reference alignment and pipeline MitoImpute. RESULTS: We aligned the sequences of 36,960 complete human mitochondrial genomes downloaded from GenBank, filtered and controlled for quality. These sequences were reformatted for use in imputation software, IMPUTE2. We assessed the imputation accuracy of MitoImpute by measuring haplogroup and genotype concordance in data from the 1000 Genomes Project and the Alzheimer's Disease Neuroimaging Initiative (ADNI). The mean improvement of haplogroup assignment in the 1000 Genomes samples was 42.7% (Matthew's correlation coefficient = 0.64). In the ADNI cohort, we imputed missing single nucleotide variants. CONCLUSION: These results show that our reference alignment and panel can be used to impute missing mtSNVs in existing data obtained from using microarrays, thereby broadening the scope of functional and clinical investigation of mtDNA. This improvement may be particularly useful in studies where participants have been recruited over time and mtDNA data obtained using different methods, enabling better integration of early data collected using less accurate methods with more recent sequence data.


Asunto(s)
ADN Mitocondrial , Polimorfismo de Nucleótido Simple , ADN Mitocondrial/genética , Frecuencia de los Genes , Genoma Humano , Estudio de Asociación del Genoma Completo , Genotipo , Humanos , Filogenia
4.
Anticancer Res ; 41(9): 4387-4393, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-34475058

RESUMEN

BACKGROUND/AIM: Breast cancer incidence is highest among women worldwide, and practical markers for personalized therapeutic strategies are few. Interleukin-12 (IL-12) is a cytokine that is reported to be significantly lower in healthy controls than breast cancer cases, however, its genotypic contribution to carcinogenesis has never been revealed in breast cancer. We examined whether IL-12A rs568408 and rs2243115 genotypes contribute to elevated breast cancer risk and summarized related literature among other cancers. MATERIALS AND METHODS: IL-12A genotypic profiles were determined among 1,232 breast cancer cases and 1,232 healthy controls via polymerase chain reaction-restriction fragment length polymorphism methodology. RESULTS: The variant genotypes of IL-12A rs568408 and rs2243115 were not found to be significantly associated with elevated breast cancer risk (both p>0.05). CONCLUSION: IL-12A rs568408 and rs2243115 genotypes may not serve as good predictors of breast cancer risk.


Asunto(s)
Neoplasias de la Mama/genética , Estudios de Asociación Genética/métodos , Subunidad p35 de la Interleucina-12/genética , Polimorfismo de Nucleótido Simple , Adulto , Estudios de Casos y Controles , Femenino , Predisposición Genética a la Enfermedad , Humanos , Persona de Mediana Edad , Polimorfismo de Longitud del Fragmento de Restricción
5.
Medicine (Baltimore) ; 100(35): e27187, 2021 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-34477178

RESUMEN

ABSTRACT: It is well-known that microRNAs are able to regulate the expression of target mRNAs through complementary base-pairing to their 3'-untranslated regions (3'UTR) sequences. This study aimed to investigate whether single nucleotide polymorphisms resided in the 3'UTR sequences in patients with chronic hepatitis B viruses (HBV) infection are associated with the development and metastasis of hepatocellular carcinoma (HCC). Seventeen single nucleotide polymorphisms in the 3'UTR sequence of 10 genes regulated or affected by hepatitis B virus X protein were found by bioinformatics methods. Two hundred fifteen patients with HBV-related HCC and 216 patients with chronic HBV infection were recruited. Through case-control study, only found that the von Hippel-Lindau gene rs1642742 (G>A) may be associated with the occurrence and metastasis of HCC. The ORs of the frequencies of rs1642742 A allele versus G allele were 1.424 (P = .038, 95% confidence interval [CI] = 1.019-1.989) between HBV-related HCC and chronic HBV infection group and were 2.004 (P = .037, 95%CI = 1.031-3.895) between tumor metastasis and non-metastasis group, respectively. Through multivariate regression analysis, we also found that rs1642742 AA genotype was an independent risk factor for tumor metastasis (odds ratio = 2.227, 95% CI = 1.043-4.752, P = .038) in HBV-related HCC group. Our study suggested that Von Hippel-Lindau rs1642742 contributed to susceptibility to developing HCC and correlated with tumor metastasis.


Asunto(s)
Carcinoma Hepatocelular/genética , Hepatitis B Crónica/complicaciones , Neoplasias Hepáticas/genética , Proteína Supresora de Tumores del Síndrome de Von Hippel-Lindau/genética , Adulto , Carcinoma Hepatocelular/virología , Femenino , Humanos , Neoplasias Hepáticas/virología , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Polimorfismo de Nucleótido Simple
6.
World J Gastroenterol ; 27(30): 5076-5087, 2021 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-34497436

RESUMEN

BACKGROUND: Leukocytes, such as T cells and macrophages, play an important role in tumorigenesis. CC chemokine ligand (CCL) 4, which is produced by lymphocytes and macrophages, has been found to be expressed in the mucosa of the gastrointestinal tract and is a potent chemoattractant for various leukocytes. AIM: To examine CCL4 expression and its genetic polymorphism rs10491121 in patients with colorectal cancer (CRC) and evaluate their prognostic significance. METHODS: Luminex technology was used to determine CCL4 Levels in CRC tissue (n = 98), compared with paired normal tissue, and in plasma from patients with CRC (n = 103), compared with healthy controls (n = 97). Included patients had undergone surgical resection for primary colorectal adenocarcinomas between 1996 and 2019 at the Department of Surgery, Ryhov County Hospital, Jönköping, Sweden. Reverse transcription quantitative PCR was used to investigate the CCL4 gene expression in CRC tissue (n = 101). Paired normal tissue and TaqMan single nucleotide polymorphism assays were used for the CCL4 rs10491121 polymorphism in 610 CRC patients and 409 healthy controls. RESULTS: The CCL4 protein and messenger RNA expression levels were higher in CRC tissue than in normal paired tissue (90%, P < 0.001 and 45%, P < 0.05, respectively). CRC tissue from patients with localized disease had 2.8-fold higher protein expression levels than that from patients with disseminated disease. Low CCL4 protein expression levels in CRC tissue were associated with a 30% lower cancer-specific survival rate in patients (P < 0.01). The level of plasma CCL4 was 11% higher in CRC patients than in healthy controls (P < 0.05) and was positively correlated (r = 0.56, P < 0.01) with the CCL4 protein level in CRC tissue. The analysis of CCL4 gene polymorphism rs10491121 showed a difference (P < 0.05) between localized disease and disseminated disease in the right colon, with a dominance of allele A in localized disease. Moreover, the rate of the A allele was higher among CRC patients with mucinous cancer than among those with non-mucinous cancer. CONCLUSION: The present study indicates that the CRC tissue levels of CCL4 and CCL4 gene polymorphism rs10491121, particularly in the right colon, are associated with clinical outcome in CRC patients.


Asunto(s)
Neoplasias Colorrectales , Polimorfismo de Nucleótido Simple , Quimiocinas CC , Neoplasias Colorrectales/genética , Humanos , Ligandos , Pronóstico
7.
Commun Biol ; 4(1): 1034, 2021 08 31.
Artículo en Inglés | MEDLINE | ID: mdl-34465887

RESUMEN

COVID-19 has caused numerous infections with diverse clinical symptoms. To identify human genetic variants contributing to the clinical development of COVID-19, we genotyped 1457 (598/859 with severe/mild symptoms) and sequenced 1141 (severe/mild: 474/667) patients of Chinese ancestry. We further incorporated 1401 genotyped and 948 sequenced ancestry-matched population controls, and tested genome-wide association on 1072 severe cases versus 3875 mild or population controls, followed by trans-ethnic meta-analysis with summary statistics of 3199 hospitalized cases and 897,488 population controls from the COVID-19 Host Genetics Initiative. We identified three significant signals outside the well-established 3p21.31 locus: an intronic variant in FOXP4-AS1 (rs1853837, odds ratio OR = 1.28, P = 2.51 × 10-10, allele frequencies in Chinese/European AF = 0.345/0.105), a frameshift insertion in ABO (rs8176719, OR = 1.19, P = 8.98 × 10-9, AF = 0.422/0.395) and a Chinese-specific intronic variant in MEF2B (rs74490654, OR = 8.73, P = 1.22 × 10-8, AF = 0.004/0). These findings highlight an important role of the adaptive immunity and the ABO blood-group system in protection from developing severe COVID-19.


Asunto(s)
COVID-19/etnología , COVID-19/genética , Grupos Étnicos/genética , Estudio de Asociación del Genoma Completo , Predisposición Genética a la Enfermedad/genética , Humanos , Intrones/genética , Polimorfismo de Nucleótido Simple
9.
Saudi Med J ; 42(9): 969-974, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-34470834

RESUMEN

OBJECTIVES: To identify ribosome protein L5 gene variants and the risk of hepatic vein thrombosis in Saudi patients. METHODS: A case-control study was conducted during the period of May 2018 to September 2019. Sixty-five patient cases of hepatic vein thrombosis (HVT) were chosen, and 50 healthy individuals of the same ages and both gender were set as a control group. The genotype of the gene RPL5 was determined by PCR please provide abbreviation in full and capillary electrophoresis. Sanger sequencing for genetically screened variants was applied for the RPL5 gene. RESULTS: Alleles A at variant rs182018447 and T allele at variant rs559377519 were strongly corelated (p=0.009 and p=0.037, respectively) with the risk of HVT. The genotype frequencies of the RPL5 gene, the A/A genotypes at rs182018447 and T/T at rs559377519 were associated with HVT (p=0.000 and p=0.004; respectively) and an increase in risk for HVT among these patients. Please rephrase the highlighted text without using the word respectively. CONCLUSION: Our findings indicate that the 5 genetic novel variants examined in the RPL5 gene were associated with a risk of HVT in all our Saudi cases. Additionally, the A/A at rs182018447 and T/T at rs559377519 genotypes were substantially susceptible to HVT in all these patients.


Asunto(s)
Síndrome de Budd-Chiari , Proteínas Ribosómicas/genética , Alelos , Estudios de Casos y Controles , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Polimorfismo de Nucleótido Simple , Arabia Saudita/epidemiología
10.
BMC Res Notes ; 14(1): 346, 2021 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-34481515

RESUMEN

OBJECTIVE: Studies on the genetic background of patients with multiple myeloma (MM) have been increasing; two important factors considered in such works are uncoupling protein-2 (UCP-2) and nuclear receptor subfamily 3 group C member 1 (NR3C1). We aim to reveal the association of MM with NR3C1 and UCP-2 gene polymorphisms. In this prospective study, 200 patients diagnosed between January 2009 and 2018 and 200 healthy individuals were included. For patients who had undergone autologous stem cell transplantation and control subjects, we statistically compared the CC, GC, and GG genotypes and the C and G alleles of the NR3C1 gene, as well as the AA, AG, and GG genotypes and the A and G alleles of the UCP-2 gene. RESULTS: While the AA genotype was significantly more common in the MM group (p = 0.001), the GG genotype was significantly more common in the control group (p = 0.016). Overall survival was found to be significantly shorter in patients with the UCP-2 GG genotype (p = 0.034). It was also found that having the GG genotype of the UCP-2 gene was a 2.48-fold risk factor for mortality. The fact that overall survival is significantly shorter in MM patients with the UCP-2 GG genotype and its definition as a risk factor for mortality have been put forward for the first time in the literature.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Mieloma Múltiple , Receptores de Glucocorticoides , Proteína Desacopladora 2 , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Mieloma Múltiple/genética , Mieloma Múltiple/terapia , Polimorfismo de Nucleótido Simple , Estudios Prospectivos , Receptores de Glucocorticoides/genética , Trasplante Autólogo , Resultado del Tratamiento , Proteína Desacopladora 2/genética
11.
Nat Commun ; 12(1): 5251, 2021 09 02.
Artículo en Inglés | MEDLINE | ID: mdl-34475392

RESUMEN

DNA methylation (DNAm) is an epigenetic regulator of gene expression and a hallmark of gene-environment interaction. Using whole-genome bisulfite sequencing, we have surveyed DNAm in 344 samples of human postmortem brain tissue from neurotypical subjects and individuals with schizophrenia. We identify genetic influence on local methylation levels throughout the genome, both at CpG sites and CpH sites, with 86% of SNPs and 55% of CpGs being part of methylation quantitative trait loci (meQTLs). These associations can further be clustered into regions that are differentially methylated by a given SNP, highlighting the genes and regions with which these loci are epigenetically associated. These findings can be used to better characterize schizophrenia GWAS-identified variants as epigenetic risk variants. Regions differentially methylated by schizophrenia risk-SNPs explain much of the heritability associated with risk loci, despite covering only a fraction of the genomic space. We provide a comprehensive, single base resolution view of association between genetic variation and genomic methylation, and implicate schizophrenia GWAS-associated variants as influencing the epigenetic plasticity of the brain.


Asunto(s)
Metilación de ADN , Genoma Humano , Sitios de Carácter Cuantitativo/genética , Esquizofrenia/genética , Factores de Edad , Encéfalo/metabolismo , Encéfalo/patología , Islas de CpG/genética , Epigénesis Genética , Predisposición Genética a la Enfermedad/genética , Variación Genética , Estudio de Asociación del Genoma Completo , Genotipo , Humanos , Polimorfismo de Nucleótido Simple
12.
Nat Commun ; 12(1): 5242, 2021 09 02.
Artículo en Inglés | MEDLINE | ID: mdl-34475398

RESUMEN

Genome-wide association studies (GWAS) have linked single nucleotide polymorphisms (SNPs) at >250 loci in the human genome to type 2 diabetes (T2D) risk. For each locus, identifying the functional variant(s) among multiple SNPs in high linkage disequilibrium is critical to understand molecular mechanisms underlying T2D genetic risk. Using massively parallel reporter assays (MPRA), we test the cis-regulatory effects of SNPs associated with T2D and altered in vivo islet chromatin accessibility in MIN6 ß cells under steady state and pathophysiologic endoplasmic reticulum (ER) stress conditions. We identify 1,982/6,621 (29.9%) SNP-containing elements that activate transcription in MIN6 and 879 SNP alleles that modulate MPRA activity. Multiple T2D-associated SNPs alter the activity of short interspersed nuclear element (SINE)-containing elements that are strongly induced by ER stress. We identify 220 functional variants at 104 T2D association signals, narrowing 54 signals to a single candidate SNP. Together, this study identifies elements driving ß cell steady state and ER stress-responsive transcriptional activation, nominates causal T2D SNPs, and uncovers potential roles for repetitive elements in ß cell transcriptional stress response and T2D genetics.


Asunto(s)
Diabetes Mellitus Tipo 2/genética , Estrés del Retículo Endoplásmico/genética , Células Secretoras de Insulina/patología , Polimorfismo de Nucleótido Simple , Activación Transcripcional/genética , Alelos , Animales , Línea Celular , Cromatina/metabolismo , Diabetes Mellitus Tipo 2/patología , Estudio de Asociación del Genoma Completo , Humanos , Ratones , Sitios de Carácter Cuantitativo , Elementos de Nucleótido Esparcido Corto/genética
13.
BMC Bioinformatics ; 22(1): 425, 2021 Sep 07.
Artículo en Inglés | MEDLINE | ID: mdl-34493206

RESUMEN

BACKGROUND: Interactions of single nucleotide polymorphisms (SNPs) and environmental factors play an important role in understanding complex diseases' pathogenesis. A growing number of SNP-environment studies have been conducted in the past decade; however, the statistical methods for evaluating SNP-environment interactions are still underdeveloped. The conventional statistical approach with a full interaction model with an additive SNP mode tests one specific interaction type, so the full interaction model approach tends to lead to false-negative findings. To increase detection accuracy, developing a statistical tool to effectively detect various SNP-environment interaction patterns is necessary. RESULTS: SNPxE, a SNP-environment interaction pattern identifier, tests multiple interaction patterns associated with a phenotype for each SNP-environment pair. SNPxE evaluates 27 interaction patterns for an ordinal environment factor and 18 patterns for a categorical environment factor. For detecting SNP-environment interactions, SNPxE considers three major components: (1) model structure, (2) SNP's inheritance mode, and (3) risk direction. Among the multiple testing patterns, the best interaction pattern will be identified based on the Bayesian information criterion or the smallest p-value of the interaction. Furthermore, the risk sub-groups based on the SNPs and environmental factors can be identified. SNPxE can be applied to both numeric and binary phenotypes. For better results interpretation, a heat-table of the outcome proportions can be generated for the sub-groups of a SNP-environment pair. CONCLUSIONS: SNPxE is a valuable tool for intensively evaluate SNP-environment interactions, and the SNPxE findings can provide insights for solving the missing heritability issue. The R function of SNPxE is freely available for download at GitHub ( https://github.com/LinHuiyi/SIPI ).


Asunto(s)
Interacción Gen-Ambiente , Polimorfismo de Nucleótido Simple , Teorema de Bayes , Fenotipo
14.
Nutrients ; 13(8)2021 Jul 21.
Artículo en Inglés | MEDLINE | ID: mdl-34444650

RESUMEN

This systematic review assessed genotypes and changes in calcium homeostasis. A literature search was performed in EMBASE, Medline and CENTRAL on 7 August 2020 identifying 1012 references. Studies were included with any human population related to the topic of interest, and genetic variations in genes related to calcium metabolism were considered. Two reviewers independently screened references, extracted relevant data and assessed study quality using the Q-Genie tool. Forty-one studies investigating Single Nucleotide Polymorphisms (SNPs) in relation to calcium status were identified. Almost half of the included studies were of good study quality according to the Q-Genie tool. Seventeen studies were cross-sectional, 14 case-control, seven association and three were Mendelian randomization studies. Included studies were conducted in over 18 countries. Participants were mainly adults, while six studies included children and adolescents. Ethnicity was described in 31 studies and half of these included Caucasian participants. Twenty-six independent studies examined the association between calcium and polymorphism in the calcium-sensing receptor (CASR) gene. Five studies assessed the association between polymorphisms of the Vitamin D receptor (VDR) gene and changes in calcium levels or renal excretion. The remaining ten studies investigated calcium homeostasis and other gene polymorphisms such as the CYP24A1 SNP or CLDN14. This study identified several CASR, VDR and other gene SNPs associated with calcium status. However, to provide evidence to guide dietary recommendations, further research is needed to explore the association between common polymorphisms and calcium requirements.


Asunto(s)
Calcio/metabolismo , Polimorfismo de Nucleótido Simple , Receptores de Calcitriol/genética , Receptores Sensibles al Calcio/genética , Calcio en la Dieta/administración & dosificación , Suplementos Dietéticos , Femenino , Genotipo , Homeostasis , Humanos , Masculino
15.
Int J Mol Sci ; 22(16)2021 Aug 16.
Artículo en Inglés | MEDLINE | ID: mdl-34445492

RESUMEN

Functional characterization of cancer risk-associated single nucleotide polymorphism (SNP) identified by genome-wide association studies (GWAS) has become a big challenge. To identify the regulatory risk SNPs that can lead to transcriptional misregulation, we performed parallel reporter gene assays with both alleles of 213 prostate cancer risk-associated GWAS SNPs in 22Rv1 cells. We disclosed 32 regulatory SNPs that exhibited different regulatory activities with two alleles. For one of the regulatory SNPs, rs684232, we found that the variation altered chromatin binding of transcription factor FOXA1 on the DNA region and led to aberrant gene expression of VPS53, FAM57A, and GEMIN4, which play vital roles in prostate cancer malignancy. Our findings reveal the roles and underlying mechanism of rs684232 in prostate cancer progression and hold great promise in benefiting prostate cancer patients with prognostic prediction and target therapies.


Asunto(s)
Factor Nuclear 3-alfa del Hepatocito/metabolismo , Proteínas de la Membrana/genética , Antígenos de Histocompatibilidad Menor/genética , Polimorfismo de Nucleótido Simple , Neoplasias de la Próstata/genética , Ribonucleoproteínas Nucleares Pequeñas/genética , Proteínas de Transporte Vesicular/genética , Línea Celular Tumoral , Cromatina/metabolismo , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Predisposición Genética a la Enfermedad , Humanos , Masculino , Pronóstico , Neoplasias de la Próstata/metabolismo , Análisis de Secuencia de ARN , Análisis de Supervivencia
16.
BMC Gastroenterol ; 21(1): 310, 2021 Aug 03.
Artículo en Inglés | MEDLINE | ID: mdl-34344313

RESUMEN

BACKGROUND: Genetic variations within the regulatory region of the gene encoding NOD-like receptor pyrin domain containing 3 (NLRP3) have been associated with Crohn's Disease (CD). NLRP3 is part of the NLRP3-inflammasome that mediates the maturation of IL-1ß and IL-18. Carrying the major allele of the single nucleotide polymorphisms (SNPs) rs10733113, rs4353135 and rs55646866 is associated with an increased risk for CD. We here studied the impact of these polymorphisms on clinical characteristics in patients of the Swiss IBD Cohort Study (SIBDCS). METHODS: We included 981 Crohn's disease (CD) patients and 690 ulcerative colitis (UC) patients of the SIBDCS. We analyzed whether three CD-associated NLRP3 polymorphisms have an impact on the clinical disease course in these patients. RESULTS: In CD patients presence of the major allele (G) of rs10733113 was associated with less surgeries and lower maximal CDAI and a similar trend was observed for rs55646866 and rs4353135. Presence of the major allele of all three SNPs was negatively correlated to maximal CDAI. In UC patients homozygous genotype for the major allele (CC) for rs55646866 was associated with a higher age at diagnosis and a higher MTWAI index. Homozygous genotype for the major allele of all three polymorphisms was associated with a higher number of ambulatory visits and longer hospital stays. CONCLUSIONS: In CD patients presence of the major allele of all three polymorphisms was associated with markers of a less severe disease course, while in UC the homozygous genotype for all major alleles suggested a more severe disease activity.


Asunto(s)
Colitis Ulcerosa , Enfermedades Inflamatorias del Intestino , Estudios de Cohortes , Colitis Ulcerosa/genética , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Proteína con Dominio Pirina 3 de la Familia NLR , Proteínas NLR , Polimorfismo de Nucleótido Simple , Dominio Pirina , Suiza
17.
Microb Pathog ; 159: 105117, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-34363926

RESUMEN

Host genetics are important to consider in the role of resistance or susceptibility for developing active pulmonary tuberculosis (TB). Several association studies have reported the role of variants in STAT4 and TRAF1/C5 as risk factors to autoimmune diseases. Nevertheless, more data is needed to elucidate the role of these gene variants in infectious disease. Our data reports for the first time, variant rs10818488 in the TRAF1/C5 gene (found 47% of the population worldwide), is associated with susceptibility (OR = 1.51) to development TB. Multivariate analysis evidenced association between rs10818488 TRAF1/C5 and risk to multibacillary TB (OR = 4.18), confers increased bacteria load in the lung, indicates a decreased ability to control pathogen levels in the lung, and spread of the pathogen to new hosts. We showed that the "loss-of-function" variant in TRAF1/C5 led to susceptibility for TB by decreased production of TNF-α. Our results suggest the role of variant TRAF1/C5 in susceptibility to TB as well as in clinical presentation of multibacillary TB.


Asunto(s)
Tuberculosis Pulmonar , Factor de Necrosis Tumoral alfa , Complemento C5/genética , Predisposición Genética a la Enfermedad , Humanos , Pulmón/metabolismo , Polimorfismo de Nucleótido Simple , Factor 1 Asociado a Receptor de TNF/genética , Factor 1 Asociado a Receptor de TNF/metabolismo , Tuberculosis Pulmonar/genética , Factor de Necrosis Tumoral alfa/genética
18.
mBio ; 12(4): e0180321, 2021 08 31.
Artículo en Inglés | MEDLINE | ID: mdl-34372699

RESUMEN

Azole resistance in pathogenic Aspergillus fumigatus has become a global public health issue threatening the use of medical azoles. The environmentally occurring resistance mutations, TR34/L98H (TR34) and TR46/Y121F/T289A (TR46), are widespread across multiple continents and emerging in the United States. We used whole-genome single nucleotide polymorphism (SNP) analysis on 179 nationally represented clinical and environmental A. fumigatus genomes from the United States along with 18 non-U.S. genomes to evaluate the genetic diversity and foundation of the emergence of azole resistance in the United States. We demonstrated the presence of clades of A. fumigatus isolates: clade A (17%) comprised a global collection of clinical and environmental azole-resistant strains, including all strains with the TR34/L98H allele from India, The Netherlands, the United Kingdom, and the United States, and clade B (83%) consisted of isolates without this marker mainly from the United States. The TR34/L98H polymorphism was shared among azole-resistant A. fumigatus strains from India, The Netherlands, the United Kingdom, and the United States, suggesting the common origin of this resistance mechanism. Six percent of azole-resistant A. fumigatus isolates from the United States with the TR34 resistance marker had a mixture of clade A and clade B alleles, suggestive of recombination. Additionally, the presence of equal proportions of both mating types further suggests the ongoing presence of recombination. This study demonstrates the genetic background for the emergence of azole resistance in the United States, supporting a single introduction and subsequent propagation, possibly through recombination of environmentally driven resistance mutations. IMPORTANCE Aspergillus fumigatus is one of the most common causes of invasive mold infections in patients with immune deficiencies and has also been reported in patients with severe influenza and severe acute respiratory syndrome coronavirus 2 (SARs-CoV-2). Triazole drugs are the first line of therapy for this infection; however, their efficacy has been compromised by the emergence of azole resistance in A. fumigatus, which was proposed to be selected for by exposure to azole fungicides in the environment [P. E. Verweij, E. Snelders, G. H. J. Kema, E. Mellado, et al., Lancet Infect Dis 9:789-795, 2009, https://doi.org/10.1016/S1473-3099(09)70265-8]. Isolates with environmentally driven resistance mutations, TR34/L98H (TR34) and TR46/Y121F/T289A (TR46), have been reported worldwide. Here, we used genomic analysis of a large sample of resistant and susceptible A. fumigatus isolates to demonstrate a single introduction of TR34 in the United States and suggest its ability to spread into the susceptible population is through recombination between resistant and susceptible isolates.


Asunto(s)
Antifúngicos/farmacología , Aspergillus fumigatus/efectos de los fármacos , Aspergillus fumigatus/genética , Farmacorresistencia Fúngica/genética , Triazoles/farmacología , Aspergilosis/tratamiento farmacológico , Aspergillus fumigatus/aislamiento & purificación , Sistema Enzimático del Citocromo P-450/genética , Proteínas Fúngicas/genética , Genoma Fúngico/genética , Humanos , Pruebas de Sensibilidad Microbiana , Polimorfismo de Nucleótido Simple/genética , Estados Unidos , Secuenciación Completa del Genoma
19.
J Pak Med Assoc ; 71(7): 1832-1837, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-34410257

RESUMEN

OBJECTIVE: To find the association of single nucleotide polymorphism of hypoxia-inducible factor-1 alpha, rs11549465 (1772 Cytosine > Thymine) with metabolic syndrome, and to compare the anthropometric and biochemical variables in different genotypes of hypoxia-inducible factor-1 alpha. METHODS: The cross-sectional comparative study was conducted at the University of Health Sciences, Lahore, Pakistan, from July 2016 to April 2019, and comprised patients of metabolic syndrome selected from the Sheikh Zayed Hospital, Lahore. Healthy controls were also enrolled. Fasting venous sample was taken for the determination of study parameters. The genetic variant of hypoxia-inducible factor-1 alpha was analysed by restriction fragment length polymorphism polymerase chain reaction. Data was analysed using SPSS 22. RESULTS: Out of 400 subjects, 200(50%) each were patients and controls. The frequency of CC genotype of hypoxia-inducible factor-1 alpha Cytosine > Thymine in patients was 166(83%) and in controls 147(73.5%); CT genotype was 34(17%) and 53(26.5%) respectively, while TT genotype was not observed. There was a significant association of the C allele and CC genotype (p=0.03) with the increased risk of metabolic syndrome (p=0.02). On comparison of study variables in the two genotypes, systolic blood pressure, anthropometric and lipid parameters were significantly higher in the wild CC genotype compared to CT in the control group (p<0.05), but there was no significant difference in the patients (p>0.05). CONCLUSIONS: Major allele C of hypoxia-inducible factor-1 alpha 1772 Cytosine > Thymine was found to be associated with increased risk of metabolic syndrome.


Asunto(s)
Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Síndrome Metabólico , Estudios de Casos y Controles , Estudios Transversales , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Hipoxia , Síndrome Metabólico/epidemiología , Síndrome Metabólico/genética , Polimorfismo de Nucleótido Simple
20.
J Pak Med Assoc ; 71(8): 1954-1958, 2021 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-34418008

RESUMEN

OBJECTIVE: To investigate the single nucleotide polymorphic variations of N-acetyltransferase 2, phase-II metabolising enzyme, and associated risk factors for oral cancer. METHODS: The case-control study was conducted from November 2017 to April 2018 after approval from the Institute of Molecular Biology and Biotechnology, Bahauddin Zakariya University, Multan, Pakistan, and comprised oral cancer patients and healthy controls. Single nucleotide polymorphism of the N-acetyltransferase 2 gene associated with oral cancer was analysed. Factors assessed using tetra-primer amplification refractory mutation system polymerase chain reaction included age, smoking, naswar, betel leaves and nuts. RESULTS: Of the 201 subjects, 94(47%) were patients and 107(53%) were controls, while 108(54%) were aged 10-30 years. Single nucleotide polymorphism rs1208 of N-acetyltransferase 2 gene was primarily A803G and Lys268Arg, with allelic frequency of G/A. Age range 51-70 was significantly (p=0.00001) associated with the prevalence of oral cancer in terms of genotypic relationship with A803G. Substantial allelic association was found between the gene and oral cancer (p=0.006895). Smoking increased the cacner risk 7-fold (odds ratio: 7.0). CONCLUSIONS: The genetic variant of N-acetyltransferase 2 rs1208 was found to be significantly associated with oral cancer progression and development of associated risk factors.


Asunto(s)
Arilamina N-Acetiltransferasa , Neoplasias de la Boca , Anciano , Arilamina N-Acetiltransferasa/genética , Estudios de Casos y Controles , Humanos , Persona de Mediana Edad , Neoplasias de la Boca/epidemiología , Neoplasias de la Boca/genética , Pakistán/epidemiología , Polimorfismo de Nucleótido Simple
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...