Journal
PLOS ONE
Volume 9, Issue 6, Pages -Publisher
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0099724
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Funding
- Chang Gung Memorial hospital [CMRPG360771-3, CMRPG3B0221]
- National Science Council, Taipei Taiwan [NSC101-2314-B-182A-025-MY3, NSC102-2314-B-001-003-MY2]
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It is common to observe the clustering of chronic hepatitis B surface antigen (HBsAg) carriers in families. Intra-familial transmission of hepatitis B virus (HBV) could be the reason for the familial clustering of HBsAg carriers. Additionally, genetic and gender factors have been reported to be involved. We conducted a three-stage genome-wide association study to identify genetic factors associated with chronic HBV susceptibility. A total of 1,065 male controls and 1,623 male HBsAg carriers were included. The whole-genome genotyping was done on Illumina HumanHap550 beadchips in 304 healthy controls and HumanHap610 beadchips in 321 cases. We found that rs9277535 (HLA-DPB1, P = 4.87x10(-14)), rs9276370 (HLA-DQA2, P = 1.9x10(-12)), rs7756516 and rs7453920 (HLA-DQB2, P = 1.48610(-11) and P = 6.66x10(-15) respectively) were significantly associated with persistent HBV infection. A novel SNP rs9366816 near HLA-DPA3 also showed significant association (P = 2.58x10(-10)). The T-T-G-G-T haplotype of the five SNPs further signified their association with the disease (P = 1.48x10(-12); OR = 1.49). The T-T haplotype composed of rs7756516 and rs9276370 was more prevalent in severe disease subgroups and associated with non-sustained therapeutic response (P = 0.0262). The G-C haplotype was associated with sustained therapeutic response (P = 0.0132; OR = 2.49). We confirmed that HLA-DPB1, HLA-DQA2 and HLA-DQB2 loci were associated with persistent HBV infection in male Taiwan Han-Chinese. In addition, the HLA-DQA2 and -DQB2 complex was associated with clinical progression and therapeutic response.
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