白细胞介素-18基因启动子区单核苷酸多态性与慢性丙型肝炎患者干扰素应答关系的研究  

Relationship of single nucleotide polymorphism in interleukin-18 gene promoter region and response to interferon treatment in patients with chronic hepatitis C

作　　者：吉木斯[1] 那顺巴雅尔[1] 贾因棠[1] 

机构地区：[1]山西医科大学第一医院感染科,太原030001

出　　处：《中华临床感染病杂志》2013年第3期148-152,共5页Chinese Journal of Clinical Infectious Diseases

基　　金：山西省回国留学人员科研资助项目

摘　　要：目的 探讨白细胞介素18(IL-18)基因启动子区-607C/A和-137G/C位点的单核苷酸多态性(SNP)与慢性丙型肝炎患者干扰素(IFN)疗效间的关系.方法 选取2005年9月23日至2012年8月20日山西医科大学第一医院感染科收治的199例慢性丙型肝炎患者,另选取180名健康人群作为对照.199例患者均采用普通IFNα或聚乙二醇干扰素α(PegIFNα)联合利巴韦林治疗.应用聚合酶链反应(PCR)及限制性片段长度多态性(RFLP)方法检测2组人群IL-18基因启动子区-607 C/A及-137G/C位点的基因型,采用x2检验分析-607C/A和-137G/C位点的基因型和等位基因分布频率,及以上两个位点的SNP与IFN治疗后获得持续病毒学应答(SVR)之间的关系.结果 慢性丙型肝炎组中IL-18基因启动子区-137GG基因型和-137G等位基因的分布频率显著高于健康对照组(x2 =6.612和6.476,P=0.010和0.011),而-137GC基因型分布频率低于健康对照组(x2=5.548,P=0.019).-607位点为AA基因型的慢性丙型肝炎患者经IFN治疗后获得SVR率显著高于CA和CC基因型患者(x2 =4.195和5.230,P=0.041和0.022),且-607位点为A等位基因的患者获得SVR率显著高于C等位基因的患者(x2 =5.903,P =0.015).-137位点为GC基因型的患者获得SVR率显著高于GG基因型患者(x2 =5.869,P=0.015),且-137位点为C等位基因的患者获得SVR率显著高于G等位基因患者(x2=3.885,P=0.049).结论 IL-18基因启动子区-137位点G等位基因可能与HCV的遗传易感性有关.-607AA和-137GC基因型患者容易获得SVR,-607位点A等位基因及-137位点C等位基因有助于慢性丙型肝炎患者经IFN抗病毒治疗后获得SVR.Objective To investigate the relationship of the single nucleotide polymorphism (SNP) of interleukin-18 (IL-18) gene promoter region-607C/A and-137G/C loci and response to interferon (IFN) treatment in patients with chronic hepatitis C (CHC).Methods A total of 199 CHC patients received combination therapy of IFNα or PegIFNα and Ribavirin in the First Affiliated Hospital,Shanxi Medical University from September 23rd,2005 to August 20th,2012 were enrolled.And 180 healthy subjects were recruited as controls.The SNPs of IL-18 gene promoter region-607C/A and-137G/C loci were detected by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP).Genotype distribution,allele frequency,and the relationships between SNPs in-607C/A and-137G/C loci and response to IFN treatment were analyzed byx2 test.Results-137GG genotype distribution and-137G allele frequency were significantly higher in CHC patients than those in healthy controls (x2 =6.612 and 6.476,P =0.010 and 0.011),whereas-137GC genotype was the opposite (x2 =5.548,P =0.019).Patients with -607AA genotype had higher sustained virological responses (SVRs) to IFN treatment compared with those with-607CA or-607CC genotypes (x2 =4.195 and 5.230,P =0.041 and 0.022).And patients with -607A allele had higher SVRs to IFN treatment compared with those with-607C allele (x2 =5.903,P =0.015).Patients with-137GC genotype had higher SVR to IFN treatment compared with those with-137GG genotype (x2 =5.869,P =0.015),and patients with-137C allele had higher SVRs to IFN treatment compared with those with-137G allele (x2 =3.885,P =0.049).Conclusions Patients with-607AA and -137GC genotypes have higher SVRs to IFN treatment than those with other genotypes.-137G allele seems to be associated with the susceptibility to HCV infection,while-607A and-137C alleles may be correlated with higher SVR to IFN treatment.

关 键 词：肝炎 丙型 慢性 白细胞介素18 多态性 单核苷酸 干扰素 

分 类 号：R512.63[医药卫生—内科学]