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Strong influence of human leukocyte antigen (HLA)‐DP gene variants on development of persistent chronic hepatitis B virus carriers in the Han Chinese population
Author(s) -
Guo Xiuchan,
Zhang Yong,
Li Ji,
Ma Jingchen,
Wei Zuli,
Tan Wenjie,
O'Brien Stephen J.
Publication year - 2011
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.24048
Subject(s) - single nucleotide polymorphism , linkage disequilibrium , human leukocyte antigen , hepatitis b virus , genome wide association study , immunology , locus (genetics) , snp genotyping , haplotype , population , genotyping , biology , snp , genetic association , virology , medicine , allele , genetics , virus , genotype , antigen , gene , environmental health
Abstract Chronic hepatitis B virus (HBV) infection is a major health issue, especially in Asia. A recent genome‐wide association study (GWAS) implicated genetic variants in the human leukocyte antigen ( HLA )‐ DP locus associated with chronic hepatitis B in Japanese and Thai populations. To confirm whether the polymorphisms at the HLA‐DP genes are associated with persistent chronic HBV infection in Han Chinese, we conducted an independent case‐control study using 521 persistent chronic HBV carriers and 819 controls that included 571 persons with HBV natural clearance and 248 never HBV‐infected (healthy) individuals. Eleven single nucleotide polymorphisms (SNPs) in a region including HLA‐DPA and HLA‐DPB and an adjacent SNP in strong linkage disequilibrium (LD) with a neighboring HLA‐DR13 locus were genotyped using the TaqMan SNP genotyping assay. Eleven variants at HLA‐DP showed a strong association with persistent chronic HBV carrier status ( P = 1.82 × 10 −12 to 0.01). We also stratified the analysis by HBV clearance status to test the association between these polymorphisms and HBV natural clearance; similar results were obtained ( P = 2.70 × 10 −11 to 0.003). Included SNPs define highly structured haplotypes that were also strongly associated with HBV chronic infection (block 1: odds ratio [OR] = 0.54, P = 8.73 × 10 −7 ; block 2: OR = 1.98, P = 1.37 × 10 −10 ). These results further confirm that genetic variants in the HLA‐DP locus are strongly associated with persistent HBV infection in the Han Chinese population. (H EPATOLOGY 2011;53:422‐428)