<i>TNFRSF4</i>和<i>TNFSF4</i>基因多态性与HCV感染关系

符祖强; 葛志军; 黄鹏; 汪春晖; 侯炜; 王炎; 张云; 岳明

doi:10.11847/zgggws1129981

摘要:

目的探讨肿瘤坏死因子受体超家族4（TNFRSF4）rs17568和肿瘤坏死因子超家族4（TNFSF4）rs3850641位点单核苷酸多态性（SNP）与丙型肝炎病毒（HCV）感染的关系，为丙型肝炎的筛查、诊断和预防提供临床依据。

方法采用病例对照研究方法抽取2011年10月 — 2015年5月在江苏省9家医院治疗的肾透析患者、20个自然村的既往有偿献血者和南京市公安局强制戒毒所的静脉吸毒人群共2 960人，将其中1 269例HCV抗体阳性者和1 691名HCV抗体阴性者分别作为病例组和对照组，每人抽取5 mL空腹静脉血，采用TaqMan-MGB探针实时荧光定量PCR方法进行基因分型，并应用单因素和多因素logistic回归模型分析TNFRSF4 rs17568和TNFSF4 rs3850641位点基因多态性与HCV感染的关系。

结果病例组TNFRSF4 rs17568 AA、AG和GG型基因型携带者分别占46.69 %、43.05 % 和10.26 %，对照组分别占44.87 %、44.44 % 和10.68 %；病例组TNFSF4 rs3850641 AA、AG和GG型基因型携带者分别占66.09 %、30.53 % 和3.37 %，对照组分别占71.89 %、26.01 % 和2.09 %；在调整了性别、年龄、是否谷丙转氨酶（ALT）异常、是否谷草转氨酶（AST）异常和感染途径后，多因素非条件logistic回归分析结果显示，与携带TNFSF4 rs3850641 AA基因型的个体相比，携带TNFSF4 rs3850641 AG/GG基因型的个体更易感染HCV（共显性模型：OR = 1.251，95 % CI = 1.052～1.488，P = 0.011；显性模型：OR = 1.275，95 % CI = 1.077～1.509，P = 0.005）；携带rs3850641 G等位基因的数量越多，HCV的感染风险越大（相加模型：OR = 1.251，95 % CI = 1.078～1.450，P = 0.003）；未发现TNFRSF4 rs17568位点基因多态性与HCV感染有相关性（均P > 0.05）。

结论 TNFSF4 rs3850641基因多态性与HCV感染有关。

Abstract:

Objective To explore the relationship between tumor necrosis factor receptor superfamily 4 (TNFRSF4) rs17568 and tumor necrosis factor superfamily 4 (TNFSF4) rs3850641 gene polymorphism and hepatitis C virus (HCV) infection and to provide clinical evidences for screening, diagnosis and prevention of HCV infection.

Methods From October 2011 to May 2015, we conducted a study in Jiangsu province among 1 269 HCV antibody-positive cases and 1 691 HCV antibody-negative controls; the recruited participants included 749 renal dialysis patients (168 cases and 581 controls) in 9 hospitals, 1 741 previously paid blood donors (810 cases and 931 controls) from 20 natural villages and 470 intravenous drug users (291 cases and 179 controls) in a mandatory detoxification center sponsored by Nanjing Municipal Public Security Bureau. Fasting venous blood samples (5 mL for each) were collected from all the participants for the genotyping of TNFRSF4 rs17568 and TNFSF4 rs3850641 with TaqMan-MGB probe real-time fluorescent quantitative PCR method. Univariate and multivariate logistic regression models were used to analyze the relationship between TNFRSF4 rs17568 and TNFSF4 rs3850641 gene polymorphisms and HCV infection.

Results In the cases, TNFRSF4 rs17568 AA, AG and GG genotype carriers accounted for 46.69%, 43.05% and 10.26%, while in the controls those genotype carriers accounted for 44.87%, 44.44% and 10.68%; the TNFSF4 rs3850641 AA, AG and GG genotype carriers accounted for 66.09%, 30.53% and 3.37% in the cases but accounted for 71.89%, 26.01% and 2.09% in controls, respectively. After adjusting for gender, age, alanine aminotransferase (ALT) abnormality, aspartate aminotransferase (AST) abnormality and route of HCV infection, unconditional multivariate logistic regression analysis demonstrated that the individuals carrying TNFSF4 rs3850641 AG/GG genotype were more susceptible to HCV compared with those carrying TNFSF4 rs3850641 AA genotype (codominant model: odds ratio OR = 1.251, 95% confidence interval 95% CI: 1.052 – 1.488, P = 0.011; dominant model: OR = 1.275, 95% CI: 1.077 – 1.509, P = 0.005); the individuals with rs3850641 G allele had an increased risk of HCV infection (additive model: OR = 1.251, 95% CI: 1.078 – 1.450, P = 0.003). No correlation was observed between TNFRSF4 rs17568 gene polymorphism and HCV infection (all P > 0.05).

Conclusion TNFSF4 rs3850641 gene polymorphism is associated with HCV infection.

TNFRSF4和TNFSF4基因多态性与HCV感染关系

Relationship between TNFRSF4 and TNFSF4 gene polymorphisms and hepatitis C virus infection