CD8+ T淋巴细胞抑制基因多态性与HBV突变的相互作用对慢性HBV感染进展的影响

Influence of interaction between the polymorphisms of CD8+ T cell inhibitory genes and hepatitis B virus mutations on the progression of chronic hepatitis B virus infection

摘要:

目的：探索与HBV（hepatitis B virus，HBV）亚型相关的CD8+ T淋巴细胞抑制性基因多态性与病毒突变的相互作用对HBV感染结局的影响。方法：总共纳入239例健康对照（healthy controls，HC）者，429例自发清除（spontaneous clearance，SR）患者，858例慢性HBV感染（chronic HBV infection，CH）患者。从5个CD8+ T淋巴细胞抑制性基因中挑选出28个标签SNP（tagging SNP，tgSNP）进行基因分型。采用直接测序确定HBV病毒突变。结果：CD8+ T淋巴细胞抑制性基因多态性（CD244中的rs485618，rs4656942，rs3766377和BIM中的rs6746608）与HBV突变（T53C，A166C，T216C，A293G，A1762T，G1764A和A1762T / G1764A）的相互作用显著影响肝硬化（liver cirrhosis，LC）或肝细胞癌（hepatocellular carcinoma，HCC）发生的风险。在多因素降维分析法（multifactor dimensionality reduction，MDR）分析中发现类似结果。结论：CD244和BIM的基因多态性可能参与调节肝硬化或肝细胞癌相关HBV突变的免疫选择，并且其相互作用可能影响慢性HBV感染进展。

Abstract:

Objective：To investigate the interaction between the polymorphisms of hepatitis B virus（HBV）-related CD8+ T cell in－hibitory genes and HBV mutations and its influence on the outcome of HBV infection. Methods：A total of 239 healthy controls，429 patients with spontaneous clearance，and 858 patients with chronic HBV infection were enrolled. A total of 28 tagging single nucleotide polymorphisms were selected from 5 CD8+ T cell inhibitory genes for genotyping. Direct sequencing was performed to determine HBV mutations. Results：The interactions between the polymorphisms of CD8+ T cell inhibitory genes（rs485618，rs4656942，and rs3766377 in CD244 and rs6746608 in BIM） and HBV mutations（T53C，A166C，T216C，A293G，A1762T，G1764A，and A1762T/G1764A） had a great influence on the risk of liver cirrhosis（LC） or hepatocellular carcinoma（HCC）. Similar results were obtained by multifactor dimensionality reduction analysis. Conclusion：The polymorphisms of CD244 and BIM genes might be involved in the regulation of immune selection of LC- or HCC-related HBV mutations，and the interactions between them may affect the progression of chronic HBV infection.