Dataset Information

Sex hormone pathway gene polymorphisms are associated with risk of advanced hepatitis C-related liver disease in males.

ABSTRACT:

Background

Males have excess advanced liver disease and cirrhosis risk including from chronic hepatitis C virus (HCV) infection though the reasons are unclear.

Goal

To examine the role variants in genes involved in androgen and estrogen biosynthesis and metabolism play in HCV-related liver disease risk in males.

Methods

We performed a cross-sectional study evaluating single nucleotide polymorphisms (SNPs) in 16 candidate genes involved in androgen and estrogen ligand and receptor synthesis and risk of advanced hepatic fibrosis (F3/F4-F4) and inflammation (A2/A3-A3). We calculated adjusted odds ratios (ORs) using logistic regression and used multifactor dimensionality reduction (MDR) analysis to assess for gene-environment interaction.

Results

Among 466 chronically HCV-infected males, 59% (n = 274) had advanced fibrosis and 54% (n = 252) had advanced inflammation. Nine of 472 SNPs were significantly associated with fibrosis risk; 4 in AKR1C3 (e.g., AKR1C3 rs2186174: ORadj = 2.04, 95% CI 1.38-3.02), 1 each in AKR1C2 and ESR1, and 1 in HSD17B6. Four SNPs were associated with inflammation risk, 2 in SRD5A1 (e.g., SRD5A1 rs248800: ORadj = 1.86, 95% CI 1.20-2.88) and 1 each in AKR1C2 and AKR1C3. MDR analysis identified a single AKR1C3 locus (rs2186174) as the best model for advanced fibrosis; while a 4-locus model with diabetes, AKR1C2 rs12414884, SRD5A1 rs6555406, and SRD5A1 rs248800 was best for inflammation.

Conclusions

The consistency of our findings suggests AKR1C isoenzymes 2 and 3, and potentially SRD5A1, may play a role in progression of HCV-related liver disease in males. Future studies are needed to validate these findings and to assess if similar associations exist in females.

SUBMITTER: White DL

PROVIDER: S-EPMC4214264 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Sex hormone pathway gene polymorphisms are associated with risk of advanced hepatitis C-related liver disease in males.

White Donna L DL Liu Yanhong Y Garcia Jose J El-Serag Hashem B HB Jiao Li L Tsavachidis Spiridon S Franco Luis M LM Lee Ju-Seog JS Tavakoli-Tabasi Shahriar S Moore David D Goldman Radoslav R Kuzniarek Jill J Ramsey David J DJ Kanwal Fasiha F Marcelli Marco M

International journal of molecular epidemiology and genetics 20141022 3

<h4>Background</h4>Males have excess advanced liver disease and cirrhosis risk including from chronic hepatitis C virus (HCV) infection though the reasons are unclear.<h4>Goal</h4>To examine the role variants in genes involved in androgen and estrogen biosynthesis and metabolism play in HCV-related liver disease risk in males.<h4>Methods</h4>We performed a cross-sectional study evaluating single nucleotide polymorphisms (SNPs) in 16 candidate genes involved in androgen and estrogen ligand and re ...[more]

PMID: 25379136

Similar Datasets

Project description:AimTo analyze the role of rs12979860 and rs8099917 polymorphisms in hepatitis C virus (HCV) genotype 1 infection of Brazilians.MethodsA total of 145 adult patients diagnosed with genotype 1 chronic hepatitis C (CHC) who had completed a 48-wk regimen of pegylated-interferon α-2a or -2b plus ribavirin combination therapy were recruited from six large urban healthcare centers and 199 healthy blood donors (controls) from a single site between January 2010 and January 2012. Data on the patients' response to treatment was collected. Polymerase chain reaction-restriction fragment length polymorphism genotyping of the interleukin (IL)28B gene fragment encompassing the single nucleotide polymorphisms (SNPs) rs12979860 (C/T) and rs8099917 (T/G) was carried out for 79 of the CHC patients and 199 of the controls. Bi-directional amplicon sequencing of the two SNPs was carried out for the remaining 66 CHC patients.ResultsSNP rs12979860 genotyping was successful in 99.5% of the controls and 97.2% of the CHC patients, whereas the SNP rs8099917 genotyping was successful in 95.5% of the controls and 100% of the CHC patients. The genotype and allele distributions for both rs12979860 and rs8099917 were significantly different between the control and CHC patient groups, with significantly higher genotype frequencies of CC and TT in the controls (P = 0.037 and 0.046, respectively) and of TT and GG in the CHC patients (P = 0.0009 and 0.0001, respectively). Analysis of the CHC patients who achieved sustained virological response (SVR) to treatment (n = 55) indicated that the rs12979860 C allele and CC genotype were predictors of SVR (P = 0.02). No significant correlation was found between rs8099917 genotypes and treatment response, but carriers of the T allele showed significantly higher rates of SVR (P = 0.02). Linkage disequilibrium analysis of the group that achieved SVR showed a significant association between rs12979860 and rs8099917 (P = 0.07).ConclusionThe higher allele frequency of rs12979860 C and rs8099917 T observed in non-HCV-infected individuals may indicate a potential protective role for these IL28B-related polymorphisms.

Dataset Information

Sex hormone pathway gene polymorphisms are associated with risk of advanced hepatitis C-related liver disease in males.

Background

Goal

Methods

Results

Conclusions

Publications

Sex hormone pathway gene polymorphisms are associated with risk of advanced hepatitis C-related liver disease in males.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets