程序性细胞死亡受体1基因多态性与慢性HCV感染及抗病毒疗效的关系

Association of programmed cell death-1 gene polymorphisms with chronic hepatitis C virus infection and antiviral effect

目的探明程序性细胞死亡受体1（PD-1）基因单核苷酸多态性（SNP）与慢性HCV感染及IFN联合利巴韦林抗HCV疗效的关系。方法选择2010年10月-2012年10月在河北省7家医院住院的慢性丙型肝炎（CHC）患者228例,采用IFN联合利巴韦林个体化方案进行抗病毒治疗,健康体检者81例作为对照组。Taq Man探针法检测PD-1基因多态性,分析患者及对照组PD-1.1及PD-1.3位点等位基因及基因型分布差异,并分析PD-1.1及PD-1.3位点SNP与抗HCV疗效的关系。计数资料组间比较采用χ~2检验。结果 CHC患者组PD-1.1位点T等位基因、TT基因型携带率显著高于对照组（52.41%vs 43.21%,χ~2=4.059,P=0.044;28.51%vs 14.81%,χ~2=6.469,P=0.039）;PD-1.1位点等位基因型分布在是否获得完全早期病毒学应答、是否获得持续病毒学应答的患者间差异均无统计学意义（P值均〉0.05）。PD-1.3位点在CHC患者及对照组均为CC型。结论 PD-1.1位点T等位基因可能与HCV慢性感染有关,TT基因型携带者HCV慢性感染风险可能较高。PD-1.1位点基因多态性与抗HCV治疗病毒学应答无明确关系。

Objective To investigate the association of single nucleotide polymorphisms（ SNPs） of programmed cell death- 1（ PD- 1）gene with chronic hepatitis C virus（ HCV） infection and the effect of antiviral therapy with interferon combined with ribavirin. Methods A total of 228 patients with chronic hepatitis C（ CHC） who were hospitalized in seven hospitals in Hebei Province,China from October 2010 to October 2012 were enrolled and treated with interferon combined with ribavirin as the individualized antiviral therapy. Eighty- one persons who underwent physical examination were enrolled as control group. The Taq Man probe method was used to detect PD- 1 gene polymorphisms. The distribution of alleles and genotypes at PD- 1. 1 and PD- 1. 3 were compared between the two groups,and the association between the SNPs of PD- 1. 1 and PD- 1. 3 and anti- HCV effect was analyzed. The chi- square test was used for the comparison of categorical data between groups. Results The CHC group showed significantly higher frequencies of T allele and TT genotype at PD- 1. 1 than the control group（ 52. 41% vs 43. 21%,χ~2= 4. 059,P = 0. 044; 28. 51% vs 14. 81%,χ~2= 6. 469,P = 0. 039）. The SNPs of PD- 1. 1 gene were not significantly associated with complete early virologic response or sustained virologic response（ both P〉 0. 05）. Both groups had CC genotype at PD- 1. 3. Conclusion PD- 1. 1 T allele might be associated with chronic HCV infection,and patients carrying TT genotype have a high risk of chronic HCV infection. PD- 1. 1 polymorphism is not associated with virologic response to anti- HCV therapy.