PTPRD rs2279776及其与HBV变异的交互作用对肝细胞癌风险的影响

摘要

目的 探讨PTPRD遗传多态性rs2279776及萁与HBV变异的交互作用和肝细胞癌(HCC)发生风险的关联性.方法 采用实时定量PCR对1012例健康对照(对照组)、990例非肝细胞癌HBV感染者(非癌HBV感染组)及1021例乙型肝炎后肝细胞癌患者(HCC组)进行PTPRDrs2279776多态性检测,应用PCR测序法分别测定HBV核心启动子区及前S区变异.采用多因素logistic回归分析rs2279776、HBV变异及它们之间的交互作用和HCC发生风险的关联性.结果 rs2279776基因型和等位基因频率的分布在HCC组与对照组之间、HCC组与非癌HBV感染组之间以及HCC组与非癌组(非癌HBV感染组+对照组)之间的差异均无统计学意义.而rs2279776GC基因型与HBV变异T1753V和preS缺失的交互作用显著增加女性HBV感染者患HCC的风险.rs2279776 GC基因型与HBV G1896A变异的交互作用可以降低HBV基因型B感染者患HCC的风险;CC基因型与HBV A1652G变异的交互作用可以显著降低基因型CHBV感染者息HCC的风险.结论 PTPRD rs2279776与HCC易感性无直接相关性,但可通过与HBV变异的交互作用对HCC发生风险产生影响.%Objective To investigate the effect of rs2279776 at the PTPRD and its interactions on hepatitis B virus (HBV) mutations as well as related risk on hepatocellular carcinoma (HCC).Methods A total of 3023 individuals,including t012 healthy controls,990 HCC-free HBV-infected subjects,and 1021 HBV-caused hepatocellular carcinoma patients (HCC) were involved in this study.PTPRD rs2279776 was genotyped,using quantitative PCR.HBV enhancer Ⅱ/basal core promoter/precore (Enh Ⅱ/BCP/preC) and preS regions were amplified by nested PCR and directly sequenced.Logistic regression analysis was performed to test the association among rs2279776 polymorphism,HBV mutations,and their interactions on the risk of HCC.Results The distributions of rs2279776 genotypes and allelic frequencies between HCC patients and healthy controls,HCC patients and HBsAg-positive subjects without HCC,HCC patients and HCC-free population (HBsAgpositive subjects without HCC and healthy controls) showed no statistically significant differences.However,the interactions of GC genotype on HBV mutations T1753V and preS deletion significantly increased on the risk of HCC in female HBV-infected subjects.Same result was also seen for rs2279776 C allele (GC + CC).The interaction of rs2279776 GC genotype with G1896A could reduce the risk of HCC in HBV genotype B infected subjects and the interaction of CC genotype with A1652G significantly reduced the risk of HCC in HBV genotype C infected subjects.Conclusion PTPRD rs2279776 did not directly contribute to the genetic susceptibility on HCC risk.However,it might affect the risk of HCC via interacting with HBV mutations.