粘病毒抵抗蛋白A和HCV基因型与干扰素治疗HCV/HIV患者早期疗效的相关分析

目的 探讨干扰素治疗慢性丙型肝炎合并艾滋病毒感染( HCV/HIV)患者早期疗效与干扰素( INF)诱导的粘病毒抵抗蛋白A(MxA)基因的单核苷酸多态性(SNP)和HCV基因型之间的关系.方法 151例HCV/HIV患者用INFα -2b联合Rib治疗24周,评价早期疗效,根据疗效将其分为早期应答与非应答组.应用PCR及限制片段长度多态性的分析方法,检测患者HCV-RNA基因分型、MxA-88及-123位点的SNP,并分析SNP与INF的早期疗效关系,HCV基因1型与非1型患者MxA基因型之间INF的早期疗效.结果 151例HCV/HIV患者除去12例HCV基因分型无记录者,139例患者中52例为HCV基因1型(34.4％),非1型87例( 57.7％)；HCV基因非1型早期应答率(85.1％)高于基因1型(55.8％),差异有统计学意义(x2=14.547,P＜0.001)；MxA启动子-88位点,GT型与GG、TT型患者疗效比较,各型间应答率GT型(79.7％)好于GG型(67.7％)及TT型(70.0％),但三者之间差异无统计学意义(x2=2.711,P＞ 0.05).MxA-123位点,CA型、CC型及AA型三者INF疗效应答率分别为78.0％、72.6％及75.0％,差异无统计学意义(x2=0.453,P＞0.05).HCV基因Ⅰ型与非1型患者MxA基因型之间INF的早期应答率比较,HCV基因非1型患者G/T、T/T型(91.5％)好于GG型(77.5％),但差异无统计学意义(x2=3.327,P=0.068),HCV基因1型患者MxA各基因型间应答率差异也无统计学意义.但是,HCV基因非1型患者与Ⅰ型患者间比较,前者G/T、T/T型(91.5％)应答率高于后者G/T、T/T型(62.5％),差异有统计学意义(P＜0.05).结论 HCV基因非1型患者MxA启动子-88、-123各基因型对INF应答率好于HCV基因1型患者,MxA-88位点为GT型的HCV/HIV患者的INF疗效较好,可为INF治疗的预后及个性化治疗提供参考依据.

The relationship of Genetic Polymorphisms of the MxA and HCV genotype with early vi- rological response to interferon for HIV/HCV co-infection

Objective To explore the relationship of host single nucleotide polymorphisms（ SNP ） of the MxA gene and HCV genotype with early virological response （ EVR ） ） to interferon for HIV/HCV coinfected patients. Methods 151 HIV/HCV co-infected patients were treated with interferon-2b （ INF- 2b ） plus ribavirin （ RBV ） for 24 weeks, then were divided into EVR group and non EVR （ NEVR ） group. HCV genotype and SNP of the MxA promoter-88 site and -123 site were examined by polymerase chain reaction-restriction fragment length polymorphism （ PCR-RFLP ） and the relationship of SNP of MxA and HCV genotype with EVR to IFN-2b were analysed. Results 12 cases were excluded because of no record of HCV genotype. Among the 139 patients, 52 cases （ 34.4% ） were genotype 1,87 cases （ 57.7% ） were non-1 genotype. The rate of EVR in was higher in genotype 1 than in non-1 genotype （ X^2=14.547, P 〈 0.001 ）; GT genotype at MxA promoter-88 responded better to INF treatment than GG and TT genotype, but the difference was not significant（ X^2=2.711, P 〉 0.05 ）. AT MxA promoter-123 site, the responses among CC , CA and AA genotype were not significantly different （ X^2==0.453, P 〉 0.05 ）. In HCV non-1 genotype patients, the rate of EVR was higher in GT and TT genotype （ 91.5% ） than in GG genotype （ 77.5% ）, but the difference was not significant （X^2==3.327,P=-0.068 ）.The rates of EVR in GT, GG and TT genotype of HCV genotype 1 patients were not significantly different. The rate of EVR in GT and TT genotype（ 91.5% ）was higher in HCV genotype 1 patients than in non-1 genotype patients（ 62.5% ）, and the difference was significant （ P 〈 0.05 ）. Conclusions Among HIV/HCV co-infected patients, those HCV non-1 genotype patients have a higher rate of EVR to INF than those genotype 1 ones, and those with GT genotype at MxA promoter-88 responds better to IFN treatment. It can be helpful in assessing the outcome and prognosis of IFN treatment.