Author:
Ashouri Saeideh,Khor Seik-Soon,Hitomi Yuki,Sawai Hiromi,Nishida Nao,Sugiyama Masaya,Kawai Yosuke,Posuwan Nawarat,Tangkijvanich Pisit,Komolmit Piyawat,Tsuiji Makoto,Shotelersuk Vorasuk,Poovorawan Yong,Mizokami Masashi,Tokunaga Katsushi
Abstract
To identify novel host genetic variants that predispose to hepatitis B virus (HBV) persistence, we performed the first genome-wide association study in the Thai population involving 318 cases of chronic hepatitis B and 309 healthy controls after quality control measures. We detected the genome-wide significant association of the HLA class II region (HLA-DPA1/DPB1, rs7770370, p-value = 7.71 × 10−10, OR = 0.49) with HBV chronicity. Subsequent HLA allele imputation revealed HLA-DPA1*01:03 (Pc = 1.21 × 10−6, OR = 0.53), HLA-DPB1*02:01 (Pc = 2.17 × 10−3, OR = 0.50), and HLA-DQB1*06:09 (Pc = 2.17 × 10−2, OR = 0.07) as protective alleles, and HLA-DPA1*02:02 (Pc = 6.32 × 10−5, OR = 1.63), HLA-DPB1*05:01 (Pc = 1.13 × 10−4, OR = 1.72), HLA-DPB1*13:01 (Pc = 4.68 × 10−2, OR = 1.60), and HLA-DQB1*03:03 (Pc = 1.11 × 10−3, OR = 1.84) as risk alleles for HBV persistence. We also detected suggestive associations in the PLSCR1 (rs35766154), PDLIM5 (rs62321986), SGPL1 (rs144998273), and MGST1 (rs1828682) loci. Among single-nucleotide polymorphisms in the PLSCR1 locus, rs1061307 was identified as the primary functional variant by in silico/in vitro functional analysis. In addition to replicating the association of the HLA class II region, we detected novel candidate loci that provide new insights into the pathophysiology of chronic hepatitis B.
Funder
Japan Agency for Medical Research and Development
Thailand Research Fund
National Research Council of Thailand
Health Systems Research Institute
Subject
Genetics (clinical),Genetics,Molecular Medicine
Cited by
4 articles.
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