干扰素诱导抗病毒蛋白基因多态性与慢性丙型肝炎疗效相关性研究  

Genetic polymorphisms of MxA protein and eIF-2α-reg2 influencing response to interferon-α treatment in patients with chronic hepatitis C

作　　者：黄雁翔[1] 马丽娜[2] 李卓[1] 林尊慧[1] 郭向华[1] 靳海英[1] 谢放[1] 陈新月[2] 

机构地区：[1]首都医科大学附属北京佑安医院北京市卫生局肝炎研究所,北京100069 [2]首都医科大学附属北京佑安医院国际医疗部,北京100069

出　　处：《实用肝脏病杂志》2008年第3期150-153,共4页Journal of Practical Hepatology

基　　金：首都医学发展科研基金(2005-3057);罗氏齐翔肝病研究基金资助项目

摘　　要：目的探讨α-干扰素(IFN-α)诱导的黏病毒抵抗蛋白(MxA)和真核细胞起始因子调节区2(eIF-2α-reg2)基因的单核苷酸多态性(SNP)与慢性丙型肝炎(CHC)患者对IFN-α治疗应答的关系。方法前瞻性研究216例CHC患者,在接受IFN-α联合利巴韦林治疗48周,随访至停药后24周时,评价疗效[分为持续性应答(SVR)和非持续性应答(NSVR)]。应用多聚酶链反应(PCR)及限制性片段长度多态性(RFLP)法检测患者MxA启动子-88(G/T)、-123(C/A)及eIF-2α-reg2(A/G)位点的SNP,并比较SNP与IFN疗效的关系。结果MxA88位点:GT与GG型患者SVR(57.43%对34.21%)比较,差异有统计学意义(x2=9.37,P<0.01);TT与GG型患者SVR(66.67%对34.21%)比较,差异有统计学意义(x2=9.37,P<0.01)。而GT与TT型患者SVR比较(57.43%对66.67%),差异无统计学意义(x2=1.00,P>0.05);MxA-123位点、eIF-2α-reg2位点基因型与IFN疗效比较:差异均无统计学意义(x2=4.87,P>0.05;x2=1.66,P>0.05)。多因素Logist回归分析结果显示:病毒载量(OR=3.178,95%CI:1.463～6.904,P=0.003)、干扰素种类(OR=3.117,95%CI:1.484～6.544,P=0.003)对SVR的独立影响具有统计学意义。MxA-88基因型(OR=1.470,95%CI:0.646～3.345,P=0.358)对SVR的独立影响无统计学意义。结论CHC患者MxA-88为TT或GT型者比GG型者对IFN-α应答好,但不是影响SVR的独立因素。Objective To identify the host single nucleotide polymorphisms （SNP）of myxovirus resistance A（MxA） protein and eukaryocyte initiation factor（eIF）-2α-reg2 and explore their relationships to the response of interferon-α therapy in patients with chronic hepatitis C. Methods 216 patients with CHC were prospectively treated with both interferon alfa or pegylated interferon-α and in combination with ribavirin for 48 weeks. After completing the therapy,the patients were followed-up for 24 weeks and the therapeutic effectiveness was evaluated. SNPs of MxA promoter 88（G/T）,-123（C/ A）and PKR-activated eIF-2α-reg2（A/G）sites were examined by polymerase chain reaction and restriction fragment length polymorphism. Results The SVR in CHC patients with GG genotype （34.21%）was lower than that in with GT genotype （57.43%,χ^2=9.37,P〈0.01）and lower than that in with TT genotype （66.67%,χ^2=10.96,P〈0.01）. There was no statistically significant difference of the SVR in CHC patients with GT and TT genotypes（57.43% vs 66.67%,χ^2=1.00,P〉0.05）. There was no statistically significant difference in IFN therapeutic effectiveness among the patients with different genotypes in MxA promoter 123,eIF-2α-reg2,respectively（χ^2=4.87,P〉0.05;χ^2=1.66,P〉0.05）. The HCV RNA load l（OR=3.178,95%CI： 1.463-6.904, P=0.003 ）and kinds of IFNα（OR=3.117,95%CI： 1.484-6.544,P=0.003）were significant for response to antiviral therapy,while the genotype of MxA promoter 88 （OR=1.470,95%CI：0.646-3.345,P=0.358）was less important. Conclusion Patients with MxA-88 TT or GT genotype infection have better therapeutic effectiveness than those with GG genotype when treated with IFNα,but the genotype of MxA promoter 88 is not an independent factor that might influence the CHC patient＇s response to IFN.

关 键 词：慢性丙型肝炎 Α-干扰素 单核苷酸多态性 黏病毒抵抗蛋白A 真核细胞起始因子 

分 类 号：R512.63[医药卫生—内科学] R587.1[医药卫生—临床医学]