Department of Gastroenterology and Hepatology, the Fourth People's Hospital of Chongqing (Chongqing Emergency Medical Center), Chongqing, China.
Institute of Life Sciences, Chongqing Medical University, Chongqing, China.
Ann Hepatol. 2018 Oct 16;17(6):940-947. doi: 10.5604/01.3001.0012.7194.
Hepatitis B virus (HBV) infection remains a public health problem worldwide. In addition, HBV infection results are influenced by various virological, immunological, and genetic factors. Inducible T-cell costimulator (ICOS) polymorphisms involving chronic HBV infection have been confirmed in previous studies. This study was to explore the effects of ICOS single nucleotide polymorphisms in HBV subtypes and their interactions with viral mutations on HBV infection outcomes.
A total of 1,636 Han Chinese individuals were recruited, including 47 asymptomatic HBV carriers (ASC), 353 chronic hepatitis B (CHB) patients, 327 HBV-related liver cirrhosis (LC) patients, 193 HBV-related hepatocellular carcinoma (HCC) patients, 464 patients with spontaneous recovery from HBV infection (SR), and 252 healthy controls (HC). DNA samples from these subjects were genotyped for four ICOS SNPs (rs11883722, rs10932029, rs1559931, and rs4675379). Direct sequencing was used to determine the HBV mutations in the enhancer II, basal core promoter, and pre-core regions.
We found that the genotype "TC" of ICOS rs10932029 SNP was associated with decreased HBV-related LC risk in the genotype C group. Additionally, the A1762T, G1764A and A1762T/G1764A mutations were associated with an increased risk of LC in the genotype C group. Further study indicated that interactions between ICOS rs10932029 genotype "TC" and A1762T or A1762T/G1764A mutations significantly decreased the LC risk in the genotype C group.
The rs10932029 genotype "TC" might be an LC-protective factor for HBV genotype C infection. The interactions between the rs10932029 genotype "TC" and A1762T or A1762T/G1764A mutations could decrease the risk of LC.
乙型肝炎病毒（HBV）感染仍是全球公共卫生问题。此外，HBV 感染结果受多种病毒学、免疫学和遗传学因素影响。先前的研究已经证实，诱导性 T 细胞共刺激物（ICOS）多态性与慢性 HBV 感染有关。本研究旨在探讨 ICOS 单核苷酸多态性在 HBV 亚型中的作用及其与病毒突变的相互作用对 HBV 感染结局的影响。
共纳入 1636 名汉族个体，包括 47 名无症状 HBV 携带者（ASC）、353 名慢性乙型肝炎（CHB）患者、327 名 HBV 相关性肝硬化（LC）患者、193 名 HBV 相关性肝细胞癌（HCC）患者、464 名 HBV 感染自发恢复（SR）患者和 252 名健康对照（HC）。对这些受试者的 DNA 样本进行了四个 ICOS 单核苷酸多态性（rs11883722、rs10932029、rs1559931 和 rs4675379）的基因分型。直接测序用于确定增强子 II、基本核心启动子和前核心区域的 HBV 突变。
我们发现，ICOS rs10932029 单核苷酸多态性的基因型“TC”与基因型 C 组 HBV 相关 LC 风险降低有关。此外，A1762T、G1764A 和 A1762T/G1764A 突变与基因型 C 组 LC 风险增加有关。进一步的研究表明，ICOS rs10932029 基因型“TC”与 A1762T 或 A1762T/G1764A 突变之间的相互作用显著降低了基因型 C 组的 LC 风险。
rs10932029 基因型“TC”可能是 HBV 基因型 C 感染的 LC 保护因素。rs10932029 基因型“TC”与 A1762T 或 A1762T/G1764A 突变之间的相互作用可降低 LC 风险。
