KIR2DL4及其配体HLA-G基因多态性与HCV易感性和慢性化关系  

Association of genetic variants of KIR2DL4 and its ligand HLA-G gene with HCV susceptibility and chronicity

作　　者：冯泽沛 陈琼 张津玮[3] 黄鹏[1,4] 尹荣 曾添[6] 贾林娜 喻荣彬 张云[1,2,4] 岳明[6] FENG Ze-pei;CHEN Qiong;ZHANG Jin-wei(Key Laboratory of Infectious Disease,Department of Epidemiology,School of Public Health,Nanjing Medical University,Nanjing,Jiangsu Province 211166,China;不详)

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传染病重点实验室,江苏南京211166 [2]东部战区疾病预防控制中心传染病防控科 [3]南京大学医学院附属鼓楼医院麻醉科 [4]南京医科大学全球健康中心 [5]江苏省肿瘤医院胸外科 [6]南京医科大学第一附属医院感染病科

出　　处：《中国公共卫生》2023年第3期335-338,共4页Chinese Journal of Public Health

基　　金：国家自然科学基金(81773499);江苏省优秀青年基金(BK20190106);云南省自然科学基金重点项目(2019FA005);新发突发呼吸系统传染病临床研究中心(HS2020002)

摘　　要：目的探讨KIR2DL4基因rs649216位点及其配体HLA-G基因rs1063320位点单核苷酸多态性(SNP)与丙型肝炎病毒(HCV)易感性和慢性化的关联性,为HCV感染预防筛查和诊断提供理论依据。方法于2011年10月-2015年12月采用整群抽样方法抽取江苏省南京市公安局强制隔离戒毒所和宜兴市强制戒毒所收治的1121例吸毒者及江苏省9家医院的733例肾透析者共1854例18~80岁未接受过抗HCV治疗(包括干扰素和直接抗病毒药物)且随访≥6个月的HCV感染高危人群进行问卷调查和HCV抗体检测,将抗-HCV和HCV RNA均为阴性的1341例作为阴性组、抗-HCV阳性且HCV RNA阴性的301例作为自限清除组、抗-HCV和HCV RNA均为阳性的212例作为持续感染组,采用TaqMan探针实时荧光定量聚合酶链式反应(PCR)进行基因分型,并应用多因素logistic回归模型分析KIR2DL4基因rs649216位点及其配体HLA-G基因rs1063320位点基因多态性与HCV易感性和慢性化的关系。结果阴性组KIR2DL4 rs649216位点CC、CT和TT型基因型携带者分别占69.15%、28.15%和2.69%,自限清除组分别占73.90%、23.05%和3.05%,持续感染组分别占62.25%、33.82%和3.92%;阴性组HLA-G rs1063320位点GG、GC和CC型基因型携带者分别占32.89%、51.25%和15.86%,自限清除组分别占34.29%、45.36%和20.36%,持续感染组分别占33.15%、47.28%和19.57%。在校正了性别、年龄、谷丙转氨酶(ALT)值是否异常、谷草转氨酶(AST)值是否异常和感染途径后,多因素非条件logistic回归分析结果显示,与携带KIR2DL4 rs649216位点CC基因型的个体相比,携带KIR2DL4 rs649216位点CT/TT基因型的个体HCV慢性化风险更高(共显性模型:OR=1.682,95%CI=1.109~2.551,P=0.014;显性模型:OR=1.671,95%CI=1.121~2.493,P=0.012);与携带KIR2DL4 rs649216位点C等位基因的个体相比,携带KIR2DL4 rs649216位点T等位基因的个体HCV慢性化风险更高(相加模型:OR=1.508,95%CI=1.070~2.125,P=0.019);与携带HLA-G rs1063320位点GG+GC基因型的�Objective To explore effects of single nucleotide polymorphism(SNP)in KIR2DL4 rs649216 and its ligand HLA-G rs1063320 on hepatitis C virus(HCV)infection susceptibility and chronicity and to provide evidence for screening,diagnosis and prevention of HCV infection.Methods Totally 1854 high-risk adults(18-80 years old)of HCV infection without the history of anti-HCV therapy(interferon or antiviral drugs treatment)were recruited with cluster sampling in two compulsory drug rehabilitation centers and hemodialysis rooms of 9 hospitals in two cities of Jiangsu province from October 2011 to December 2015;all the participants(1121 drug addicts and 733 hemodialysis patients)were assigned into three groups according to the results of two separate HCV antibody and HCV RNA detections during previous 6 months before the survey:1341 in an uninfected group(negative for both HCV antibody and HCV RNA),301 in a spontaneous HCV clearance group(positive for HCV antibody but negative for HCV RNA),and 202 in a persistent HCV infection group(positive for both HCV antibody and HCV RNA).Face-to-face questionnaire interview was conducted among the participants and fasting venous blood samples of the participants were collected for detections of HCV antibody,HCV RNA,HCV genotype,and genotype of targeted genes with TaqMan probe-based real-time quantitative PCR.Multivariate logistic regression model was adopted in analyses on the associations of SNP in KIR2DL4 rs649216 and its ligand HLA-G rs1063320 locus with HCV susceptibility and chronicity.Results The proportions for carriers of genotype CC,CT and TT of KIR2DL4 rs649216 were 69.15%,28.15%and 2.69%in the uninfected group;73.90%,23.05%and 3.05%in the spontaneous clearance group;and 62.25%,33.82%and 3.92%in the persistent infection group;while,those for carriers of genotype GG,GC and CC of HLA-G rs1063320 were 32.89%,51.25%and15.86%in the uninfected group;34.29%,45.36%and 20.36%in the spontaneous clearance group;and 33.15%,47.28%and 19.57%in the persistent infection group,respectively.After

关 键 词：丙型肝炎病毒(HCV) 易感性 慢性化 单核苷酸多态性(SNP) 

分 类 号：R183[医药卫生—流行病学]