title: Strong influence of human leukocyte antigen (HLA)-DP gene variants on development of persistent chronic hepatitis B virus carriers in the Han Chinese population.
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.
authors.affiliation: Zhejiang Provincial Key Laboratory of Medical Genetics, School of Laboratory Medicine and Life Science, Wenzhou Medical College, Zhejiang, China. xguo1@cdc.gov
authors.forename: Xiuchan
authors.initials: X
authors.lastname: Guo
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
authors.forename: Ji
authors.initials: J
authors.lastname: Li
authors.forename: Jingchen
authors.initials: J
authors.lastname: Ma
authors.forename: Zuli
authors.initials: Z
authors.lastname: Wei
authors.forename: Wenjie
authors.initials: W
authors.lastname: Tan
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: O'Brien
mesh_terms: D000328:Adult; D002353:Carrier State / Q000821:virology*; D016022:Case-Control Studies; D002681:China / Q000453:epidemiology; D005260:Female; D020022:Genetic Predisposition to Disease / Q000208:ethnology / Q000235:genetics; D006682:HLA-DP Antigens / Q000235:genetics*; D059867:HLA-DP alpha-Chains; D059868:HLA-DP beta-Chains; D006684:HLA-DR Antigens / Q000235:genetics; D059810:HLA-DR Serological Subtypes; D006239:Haplotypes / Q000235:genetics; D006515:Hepatitis B virus; D019694:Hepatitis B, Chronic / Q000453:epidemiology / Q000208:ethnology* / Q000235:genetics*; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*
chemical_list: D006682:HLA-DP Antigens; D059867:HLA-DP alpha-Chains; D059868:HLA-DP beta-Chains; C071695:HLA-DPA antigen; C071170:HLA-DPB1 antigen; D006684:HLA-DR Antigens; D059810:HLA-DR Serological Subtypes; C097337:HLA-DR13 antigen