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
Genome Medical Science Project, National Center for Global Health and Medicine, Toyama, Tokyo,Japan.
Department of Human Genetics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Front Genet. 2022 Jun 13;13:887121. doi: 10.3389/fgene.2022.887121. eCollection 2022.
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 class II region (, rs7770370, -value = 7.71 × 10, OR = 0.49) with HBV chronicity. Subsequent allele imputation revealed ( = 1.21 × 10, OR = 0.53), ( = 2.17 × 10, OR = 0.50), and ( = 2.17 × 10, OR = 0.07) as protective alleles, and ( = 6.32 × 10, OR = 1.63), ( = 1.13 × 10, OR = 1.72), ( = 4.68 × 10, OR = 1.60), and ( = 1.11 × 10, OR = 1.84) as risk alleles for HBV persistence. We also detected suggestive associations in the (rs35766154), (rs62321986), (rs144998273), and (rs1828682) loci. Among single-nucleotide polymorphisms in the locus, rs1061307 was identified as the primary functional variant by functional analysis. In addition to replicating the association of the class II region, we detected novel candidate loci that provide new insights into the pathophysiology of chronic hepatitis B.
为了鉴定出易导致乙肝病毒（HBV）持续感染的新型宿主基因变异，我们在泰国人群中开展了第一项全基因组关联研究，在进行质量控制措施后，该研究纳入了318例慢性乙型肝炎患者和309名健康对照。我们检测到II类区域（，rs7770370，-值 = 7.71 × 10，比值比 = 0.49）与HBV慢性感染存在全基因组显著关联。随后的等位基因推算显示（ = 1.21 × 10，比值比 = 0.53）、（ = 2.17 × 10，比值比 = 0.50）和（ = 2.17 × 10，比值比 = 0.07）为保护性等位基因，而（ = 6.32 × 10，比值比 = 1.63）、（ = 1.13 × 10，比值比 = 1.72）、（ = 4.68 × 10，比值比 = 1.60）和（ = 1.11 × 10，比值比 = 1.84）为HBV持续感染的风险等位基因。我们还在（rs35766154）、（rs62321986）、（rs144998273）和（rs1828682）位点检测到提示性关联。在该位点的单核苷酸多态性中，rs1061307经功能分析被确定为主要功能变异。除了重复验证II类区域的关联外，我们还检测到了新的候选位点，这些位点为慢性乙型肝炎的病理生理学提供了新的见解。
