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

作　　者：凡豪志 岳明[3] 邵建国[4] 薛红 田亭 巫晶晶 姚敏 黄鹏[1,2] 喻荣彬[1,2] 张云[1,2] FAN Hao-zhi;YUE Ming;SHAO Jian-guo;XUE Hong;TIAN Ting;WU Jing-jing;YAO Min;HUANG Peng;YU Rong-bin;ZHANG Yun(Department of Epidemiology and Biostatistics,School of Public Health,Nanjing Medical University,Nanjing 211166,China;Key Laboratory of lnfeetious Diseases,School of Public Health,Nanjing Medical University,Nanjing 211166,China;Department of Infectious Diseases,the First Affiliated Hospital of Nanjing Medical University,Nanjing 210029,China;Department of Gastroenterology,the Nantong Third Affiliated Hospital of Nantong University,Nantong 226001,China;Fourth Ward,the Nantong Third Affiliated Hospital of Nantong University,Nantong 226001,China;Department of Acute Infectious Disease Control and Prevention,Jiangsu Province Center for Disease Control and Prevention,Nanjing 210009,China;Department of Immunology,Medical School of Nantong University,Nantong 226001,China)

机构地区：[1]南京医科大学公共卫生学院流行病与卫生统计学系,江苏南京211166 [2]南京医科大学公共卫生学院传染病重点实验室,江苏南京211166 [3]南京医科大学第一附属医院感染病科,江苏南京210029 [4]南通大学附属南通大学附属南通市第三人民医院消化科,江苏南通226001 [5]南通大学附属南通大学附属南通市第三人民医院四病区,江苏南通226001 [6]江苏省疾病预防控制中心急性传染病防制所,江苏南京210009 [7]南通大学医学院免疫学系,江苏南通226001

出　　处：《中华疾病控制杂志》2018年第10期1020-1023,1027,共5页Chinese Journal of Disease Control & Prevention

基　　金：国家自然科学基金(81703273;81502853;81773499);江苏省自然科学基金(BK20151026;BK20171054);江苏省卫计委"科教强卫工程"青年医学人才项目(QNRC2016616)

摘　　要：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.

关 键 词：受体 CCR5 肝炎 丙型 慢性 多态性 单核苷酸 干扰素类 

分 类 号：R394.112[医药卫生—医学遗传学] R969.4[医药卫生—基础医学]