白细胞介素-28B的基因多态性与干扰素抗丙型肝炎病毒治疗应答的关系

Relationship of interleukin 28B polymorphisms and response to interferon treatment in patients with hepatitis C infection

目的探讨IL-28B基因多态性与慢性丙型肝炎患者对干扰素治疗应答的关系。方法采用分子生物学方法提取基因组DNA,PCR扩增后直接测序,对我院感染科门诊和住院的63例应答组(SVR)和34例无应答组(NVR)的HCV 1型患者的SNPs rs8099917和rs12980275位点进行检测分析。结果 (1)rs12980275只检测到AA、AG,rs8099917只检测到TT、TG,二者均未发现GG型。(2)rs12980275、rs8099917基因型分布在SVR组和NVR组之间差异均具有统计学意义(OR=3.288,95%CI=[1.171～9.234],χ2=5.416,P=0.020;OR=2.865,95%CI=[1.006～8.154],χ2=4.081,P=0.043)。(3)rs12980275等位基因频率在SVR组和NVR组之间差异具有统计学意义(OR=2.846,95%CI=[1.086～7.464],χ2=4.828,P=0.028);rs8099917等位基因频率在SVR组和NVR组之间差异无统计学意义(OR=2.543,95%CI=[0.953～6.785],χ2=3.664,P=0.056)。(4)rs12980275、rs8099917的基因型及等位基因频率在SVR、NVR组中的相关性分析r均大于0(r=0.236,r=0.205,r=0.158,r=0.137),均呈正相关。结论 rs12980275和rs8099917多态性对干扰素抗丙型肝炎病毒治疗应答有重要影响,可以预测抗病毒疗效,为实现个体化治疗提供依据。

Objective To determine the correlation between interleukin 28B（IL-28B） polymorphism in chronic hepatitis C patients and their response to interferon treatment.Methods A total of 97 cases of identified chronic hepatitis C 1 type,including 63 cases of sustained virological response（SVR） and 34 cases of null virological response（NVR）,were collected from in-patient and out-patient of our department from 2009 to 2011.Their genomic DNA was extracted by molecular biology methods,and PCR directly sequencing was performed for SNPs genotyping of rs8099917 and rs12980275.The SNPs genotypes of the 2 sites were analyzed in the SVR and NVR group.Results Genotype of rs12980275 was only detected as AA,and AG,while that of rs8099917 was only TT and TG.There was no GG type found in both rs12980275 and rs8099917.Significant difference was found in the genotype distribution of rs12980275 and rs8099917 between the SVR group and NVR group（OR=3.288,95%CI=[1.171 to 9.234],Pearson＇s Chi square=5.416,P=0.020;OR=2.865;95%CI= [1.006 to 8.154],Pearson＇s Chi square=4.081,P=0.043）.The frequencies of alleles of rs12980275 were significant difference between the 2 groups（OR=2.846,95%CI=[1.086 to 7.464],Pearson＇s Chi square=4.828,P=0.028）.The frequencies of alleles of rs8099917 had no significant difference between the 2 groups（OR=2.543,95%CI=[0.953 to 6.785],Pearson＇s Chi square=3.664,P=0.056）.The genotypes distribution and the frequencies of alleles of rs12980275 and rs8099917 had positive correlation between the 2 groups（Pearson＇s r=0.236;Pearson＇s r=0.205;Pearson＇s r=0.158;Pearson＇s r=0.137）.Conclusion Polymorphism of SNPs rs8099917 and rs12980275 are associated with outcomes of patients＇ antiviral response to interferon.IL-28B genetic polymorphisms can provide a reliable basis for individual therapy and predicting treatment efficacy.