Department of Statistics, Tamkang University, New Taipei City 25137, Taiwan.
Institute of Biomedical Sciences, Academia Sinica, Nankang, Taipei 11529, Taiwan.
World J Gastroenterol. 2021 Oct 7;27(37):6262-6276. doi: 10.3748/wjg.v27.i37.6262.
Genome-wide association studies from Asia indicate that HLA-DP and HLA-DQ loci are important in persistent hepatitis B virus (HBV) infections. One of the key elements for HBV-related carcinogenesis is persistent viral replication and inflammation.
To examine genetic and nongenetic factors with persistent HBV infection and viral load in families with hepatocellular carcinoma (HCC).
The HCC families included 301 hepatitis B surface antigen (HBsAg) carriers and 424 noncarriers born before the nationwide vaccination program was initiated in 1984. Five HBV-related single nucleotide polymorphisms (SNPs) - rs477515, rs9272105, rs9276370, rs7756516, and rs9277535 - were genotyped. Factors associated with persistent HBV infection and viral load were analyzed by a generalized estimating equation.
In the first-stage persistent HBV study, all SNPs except rs9272105 were associated with persistent infection. A significantly higher area under the reciprocal operating characteristic curve for nongenetic factors genetic factors ( < 0.001) suggests that the former play a major role in persistent HBV infection. In the second-stage viral load study, we added 8 HBsAg carriers born after 1984. The 309 HBsAg carriers were divided into low ( = 162) and high viral load ( = 147) groups with an HBV DNA cutoff of 10 cps/mL. Sex, relationship to the index case, rs477515, rs9272105, and rs7756516 were associated with viral load. Based on the receiver operating characteristic curve analysis, genetic and nongenetic factors affected viral load equally in the HCC family cohort ( = 0.3117).
In these east Asian adults, the mechanism of persistent HBV infection-related SNPs was a prolonged viral replication phase.
亚洲的全基因组关联研究表明，HLA-DP 和 HLA-DQ 基因座在持续性乙型肝炎病毒（HBV）感染中很重要。HBV 相关致癌的一个关键因素是持续性病毒复制和炎症。
研究与肝细胞癌（HCC）相关的遗传和非遗传因素在具有持续性 HBV 感染和病毒载量的家族中的作用。
该 HCC 家族包括 301 名乙型肝炎表面抗原（HBsAg）携带者和 424 名 1984 年全国疫苗接种计划启动前出生的非携带者。对 5 个与 HBV 相关的单核苷酸多态性（SNP）-rs477515、rs9272105、rs9276370、rs7756516 和 rs9277535-进行基因分型。通过广义估计方程分析与持续性 HBV 感染和病毒载量相关的因素。
在第一阶段持续性 HBV 研究中，除 rs9272105 外，所有 SNP 均与持续性感染相关。非遗传因素遗传因素的倒数工作特征曲线下面积差异具有统计学意义（<0.001），表明前者在持续性 HBV 感染中起主要作用。在第二阶段病毒载量研究中，我们增加了 8 名 1984 年后出生的 HBsAg 携带者。将 309 名 HBsAg 携带者分为低病毒载量（=162）和高病毒载量（=147）两组，HBV DNA 截断值为 10 cps/ml。性别、与索引病例的关系、rs477515、rs9272105 和 rs7756516 与病毒载量相关。基于接收者操作特征曲线分析，遗传和非遗传因素对 HCC 家族队列中病毒载量的影响相等（=0.3117）。
在这些东亚成年人中，持续性 HBV 感染相关 SNP 的机制是病毒复制期延长。
