Huang Peng, Zhang Yuanyuan, Lu Xiaomei, Xu Yin, Wang Jie, Zhang Yun, Yu Rongbin, Su Jing
Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, China.
Department of General Practice, Kangda College, Nanjing Medical University, Nanjing, China.
PLoS One. 2015 Apr 13;10(4):e0123513. doi: 10.1371/journal.pone.0123513. eCollection 2015.
Antigen-presentation genes play a vital role in the pathogenesis of HCV infection. However, the relationship of variants of these genes with spontaneous outcomes of HCV infection has not been fully investigated. To explore novel loci in the Chinese population, 34 tagging-SNPs in 9 candidate genes were genotyped for their associations with the outcomes of HCV infection. The distributions of different genotypes and haplotypes were compared among 773 HCV-negative controls, 246 subjects with HCV natural clearance, and 218 HCV persistent carriers recruited from hemodialysis patients and intravenous drug users. Our study implicated that TAP2, HLA-DOA, HLA-DOB, and tapasin loci were novel candidate regions for susceptibility to HCV infection and viral clearance in the Chinese population. Logistic regression analyses showed that TAP2 rs1800454 A (OR = 1.48, P = 0.002) and HLA-DOB rs2071469 G (OR = 1.23, P = 0.048) were significantly associated with increased susceptibility to establishment of HCV infection. However, high-risk behavior exposure and age were stronger predictors of HCV infection. Mutation of tapasin rs9277972 T (OR = 1.57, P =0.043) increased the risk of HCV chronicity, and HLA-DOA rs3128935 C (OR = 0.62, P = 0.019) increased the chance of viral resolution. With regards to the effect of rs3128925, interactions were found with high-risk behavior (P = 0.013) and age (P = 0.035). The risk effect of rs3128925 T for persistent HCV infection was higher in injecting drug users (vs. dialysis patients) and in subjects ≥ 40 years old (vs. < 40 years old).
抗原呈递基因在丙型肝炎病毒（HCV）感染的发病机制中起着至关重要的作用。然而，这些基因的变异与HCV感染的自发转归之间的关系尚未得到充分研究。为了在中国人群中探索新的基因位点，对9个候选基因中的34个标签单核苷酸多态性（tagging-SNP）进行基因分型，以研究它们与HCV感染转归的相关性。比较了773名HCV阴性对照者、246名HCV自然清除者以及从血液透析患者和静脉吸毒者中招募的218名HCV持续携带者中不同基因型和单倍型的分布情况。我们的研究表明，TAP2、HLA-DOA、HLA-DOB和塔帕辛（tapasin）基因位点是中国人群中HCV感染易感性和病毒清除能力的新候选区域。逻辑回归分析显示，TAP2基因的rs1800454 A（比值比[OR]=1.48，P=0.002）和HLA-DOB基因的rs2071469 G（OR=1.23，P=0.048）与HCV感染易感性增加显著相关。然而，高危行为暴露和年龄是HCV感染更强的预测因素。塔帕辛基因rs9277972 T的突变（OR=1.57，P=0.043）增加了HCV慢性化的风险，而HLA-DOA基因rs3128935 C（OR=0.62，P=0.019）增加了病毒清除的机会。关于rs3128925的作用，发现其与高危行为（P=0.013）和年龄（P=0.035）存在相互作用。rs3128925 T对HCV持续感染的风险效应在注射吸毒者（相对于透析患者）和年龄≥40岁的受试者（相对于<40岁的受试者）中更高。
