Abstract
Hepatitis B virus (HBV) infection is the predominant risk factor for chronic hepatitis B (CHB), liver cirrhosis (LC) and hepatocellular carcinoma (HCC). Recently, genome-wide association studies have identified human leukocyte antigen (HLA)-DP polymorphisms (rs3077 and rs9277535) as a new chronic HBV infection susceptibility locus. Since then, the relationship between HLA-DP polymorphisms and various outcomes of HBV infection has been reported. However, the results have been inconclusive. To derive a more precise estimation of the relationship between HLA-DP polymorphisms and various outcomes of HBV infection, a meta-analysis of 62,050 subjects from 29 case-control studies was performed. We found that rs3077 and rs9277535 in HLA-DP significantly decreased HBV infection risks and increased HBV clearance possibility in a dose-dependent manner. In the subgroup analysis by ethnicity, study design and sample size, significant associations were found for these polymorphisms in almost all comparisons. Meanwhile, haplotype analyses of the two polymorphisms revealed a significant association between the combination of these alleles and HBV infection outcomes. However, no significant results were observed in HCC development. Our results further confirm that genetic variants in the HLA-DP locus are strongly associated with reduced HBV infection and increased the likelihood of spontaneous viral clearance.
Highlights
Hepatitis B virus (HBV) infection is a major global health concern, with more than 2 billion people infected, of whom 400 million are chronic carriers[1,2]
For HBV clearance, our meta-analysis shown that individuals carrying the human leukocyte antigen (HLA)-DPA1 rs3077-A allele had a significantly higher chance of spontaneous clearance upon HBV infection (OR = 1 .51, 95% confidence intervals (CIs): 1.35–1.68, P < 10−5; Fig. 2)
Many replications studies have been conducted to explore the relationship between HLA-DP polymorphisms and various outcomes of HBV infection
Summary
Hepatitis B virus (HBV) infection is a major global health concern, with more than 2 billion people infected, of whom 400 million are chronic carriers[1,2]. A genome-wide association study (GWAS) identified two single-nucleotide polymorphism (SNPs) in HLA-DP (rs3077 and rs9277535) for persistent HBV infection in Japanese and Thai populations[13]. Many case–control studies have been carried out to investigate the role of the two SNPs in HLA-DP in relation to outcomes of HBV infection among various populations. Genetic association studies can be problematic to reproduce due to insufficient power, ethnic diversity, multiple hypothesis testing, population stratification, phenotypic heterogeneity and publication bias. We carried out a comprehensive meta-analysis on all eligible studies to estimate relationship between HLA-DP polymorphisms (rs3077 and rs9277535) and HBV infection outcomes as well as to quantify the between-study heterogeneity and potential bias
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call