CC趋化因子细胞受体5基因多态性与慢性丙肝干扰素疗效关联性的研究

Association of C-Cchemokine receptor type 5 Gene Polymorphisms with the Effectiveness of Interferon Therapy among Patients with Chronic Hepatitis C

目的探索CC趋化因子细胞受体5(C-C chemokine receptor type 5,CCR5)基因多态性与慢性丙型肝炎(chronic hepatitis C,CHC)患者治疗效果的关联,为指导今后丙肝治疗方案及预后评价提供依据。方法本研究共纳入CHC患者348例,所有患者均接受标准干扰素治疗48周并随访24周。利用Taqman-MGB探针技术,对CCR5基因上rs10800874和rs746492位点进行基因分型,分析其多态性与患者治疗效果的关系。结果经Logistic回归分析结果显示,与rs10800874 TT基因型的CHC携带者相比,TG(调整OR=1. 87,95%CI=1. 08~3. 25,P=0. 026)和GG(调整OR=1. 96,95%CI=1. 01~3. 82,P=0. 048)基因型的携带患者更容易获得持续性病毒学应答(sustained virological response,SVR)。分层分析发现,在女性、高葡萄糖水平以及低甲胎蛋白水平亚组中,携带rs10800874-G等位基因与SVR之间的仍然显著相关(所有P <0. 05)。结论 CCR5 rs10800874-G等位基因是CHC患者接受标准干扰素治疗获得SVR的保护因素。

Objective To explore the association between C-C chemokine receptor type 5（CCR5） gene polymorphisms and the effectiveness of interferon （IFN） therapy in chronic hepatitis C （CHC） patients, so as to provide a basis for guiding CHC treatment and prognosis evaluation. Methods A total of 348 CHC were included in this study. All patients received standard 48-week IFN therapy and were followed up for 24 weeks. Two single nucleotide polymorphisms （SNPs） rs10800874 and rs746492 in CCPO gene were genotyped by Taqman-MGB methods, and the relationship between the SNPs and the treatment effectiveness was analyzed. Results Logistic regression analysis showed that CHC patients carrying the rs10800874 TG （adjusted OR = 1.87, 95% CI = 1.08-3.25, P = 0. 026） and GG （adjusted OR = 1. 96, 95% CI 1.0L- 3.82, P=0. 048） genotypes were more likely to have a sustained virological response （SVR）, compared with CHC patients carrying Tr genotype. The results of further stratified analysis demonstrated that the association between carrying the rs10800874-G allele and SVR in females, high glucose levels and low alpha-fetoprotein levels remained significant （ all P 〈 0. 05）. Conclusions The CCR5 rs10800874-G allele is a protective factor for SVR among CHC patients receiving standard IFN therapy.