Strong influence of human leukocyte antigen (HLA)-DP gene variants on development of persistent chronic hepatitis B virus carriers in the Han Chinese population

Authors

  • Xiuchan Guo,

    Corresponding author
    1. Zhejiang Provincial Key Laboratory of Medical Genetics, School of Laboratory Medicine and Life Science, Wenzhou Medical College, Zhejiang, China
    2. State Key Laboratory for Infectious Diseases Prevention and Control, Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China
    3. Laboratory of Genomic Diversity, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD
    Current affiliation:
    1. 1600 Clifton Road NE, E-47, Atlanta, GA 30333
    • Zhejiang Provincial Key Laboratory of Medical Genetics, Wenzhou Medical College, Zhejiang, China
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    • fax: (404) 639-2980

  • Yong Zhang,

    1. State Key Laboratory for Infectious Diseases Prevention and Control, Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China
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  • Ji Li,

    1. Laboratory of Genomic Diversity, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD
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  • Jingchen Ma,

    1. Hebei Province's Center for Disease Control and Prevention, Shijiazhuang, China
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  • Zuli Wei,

    1. Luohe's Center for Disease Control and Prevention, Luohe City, Henan Province, China
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  • Wenjie Tan,

    1. Biotech Center for Viral Disease Emergency, Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China
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  • Stephen J. O'Brien

    1. Laboratory of Genomic Diversity, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD
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  • Potential conflict of interest: Nothing to report.

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. (HEPATOLOGY 2011;53:422-428)

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