广东地区慢性丙型肝炎患者IL28B基因多态性与抗病毒疗效的关系

摘要

目的 研究广东地区慢性丙型肝炎患者(CHC)白细胞介素28B(IL28B)基因单核苷酸多态性(single nucleotide polymorphism,SNP)的分布特点及其与抗病毒疗效之间的关系,为合理选择经济有效的个体化抗病毒治疗方案提供依据,提高CHC的治疗应答率.方法 对74例CHC患者给予聚乙二醇干扰素(PEG-IFN)联合利巴韦林(RBV)抗病毒治疗,疗程48周或72周,停药后随访24周.通过PCR测序,检测所有患者的IL28B(rs8099917、rs12979860、rs12980275)位点SNP,以快速病毒学应答率(RVR)及持续病毒学应答率(SVR)作为疗效的主要评价指标,比较IL28B不同基因型与抗病毒疗效的关系,评估IL28 BSNP在CHC患者治疗应答中的作用.结果 74例患者中,rs8099917位点基因型为TT、TG、GG各63(85.1％)、11(14.9％)、0(0％)例,rs12979860位点基因型为CC、CT、TT各60(81.1％)、14(18.9％)、0(0％)例,rs12980275位点基因型为AA、AG、GG各57 (77.0％)、17(23.0％)、0(0％)例.对HCV 1型患者,上述三个位点中仅rs12979860 CC型与SVR有关,结果有统计学差异(SVR组vs NonSVR组,88.4％ vs 58.3％,P＜0.05);对非HCV1型患者,rs8099917、rs12979860、rs12980275三个位点与RVR和SVR无关,结果无统计学差异(P＞0.05).结论 广东地区CHC患者IL28B基因rs8099917、rs12979860、rs12980275位点分别以TT、CC、AA为主;对于HCV 1型CHC患者,rs12979860位点的基因型可以作为治疗前SVR的一个重要预测因子.%Objective To investigate the genotypes of interleukin (IL) 28B polymorphism and the effect of IL28B genotypes on the responses to therapy in patients with chronic hepatitis C (CHC).Methods A total of 74 patients with CHC were prospectively treated with pegylated interferon α (PEG-IFN α) in combination with ribavirin (RBV) for 48 or 72 weeks.After finishing the therapy,the patients were followed up for 24 weeks and the therapeutic effect was evaluated with rapid virological response (RVR) and sustained virological response (SVR).The IL28B rs8099917,rs12979860 and rs12980275 were identified by sequencing the PCR products amplified from the genome DNA of each participate.The IL28 B genotypes in CHC patients were analyzed and the effect of singlenucleotide polymorphism (SNP) on responses to therapy was assessed.Result rs8099917 TT,TG,GG were 63(85.1％),11(14.9％),0(0％),respectively.rs12979860 CC,CT,TT were 60 (81.1％),14 (18.9％),0 (0％),respectively.rs12980275 AA,AG,GG were 57 (77.0％),17 (23.0％),0 (0％),respectively.In patients infected with HCV genotype-1,only rs12979860 was associated with SVR rate,and the proportion of rs12979860 CC in SVR group was significantly higher than that in non-SVR group (88.4％ vs 58.3％,P ＜ 0.05).In patients infected with HCV non genotype-1,none of the three SNPs was associated with RVR or SVR (P ＞ 0.05).Conclusions The majority of the patients with CHC carry IL28B genotype rs8099917 TT,rs12979860 CC and rs12980275 AA in Guangdong.The genotypes of IL28 B(rs12979860) is closely related to the effect of PEG-IFN α/RBV therapy,and it might be an important predictive factor for SVR before treatment in patients with CHC.