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KIR3DL1 rs35974949和rs35656676位点基因多态性与HCV易感性和慢性化关系

Association of SNP at KIR3DL1 rs35974949 and rs35656676 with HCV susceptibility and chronicity in high-risk populations

  • 摘要:
      目的  探讨KIR3DL1基因rs35974949和rs35656676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,为定制HCV感染的筛查、诊断和个体化预防策略提供理论依据。
      方法  于2008年8月 — 2015年12月采用整群抽样方法抽取江苏省句容市和丹阳市25个自然行政村1788名既往有偿献血者和江苏省9家三级医院肾透析中心749例肾透析者共2537名18~79岁未接受过抗HCV治疗(包括干扰素和直接抗病毒药物)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1512人作为阴性组、抗 – HCV阳性且HCV RNA阴性的382人作为自限清除组、抗 – HCV和HCV RNA均为阳性的643人作为持续感染组,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KIR3DL1基因rs35974949和rs35656676位点基因多态性与HCV易感性和慢性化的关系。
      结果  阴性组KIR3DL1 rs35974949位点GG、GT和TT型基因型携带者分别占78.47 %、20.05 % 和1.49 %,自限清除组分别占76.64 %、19.16 %和4.20 %,持续感染组分别占74.34 %、19.60 %和6.07 %;阴性组KIR3DL1 rs35656676位点CC、CG和GG型基因型携带者分别占31.32 %、50.60 %和18.08 %,自限清除组分别占31.68 %、49.74 %和18.59 %,持续感染组分别占31.78 %、50.47 %和17.76 %。在校正性别、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KIR3DL1 rs35974949位点GG/GT基因型的个体相比,携带KIR3DL1 rs35974949 位点TT基因型的个体更易感染HCV(共显性模型:OR = 2.802,95 % CI = 1.571~4.998,P < 0.001;隐性模型:OR = 2.860,95 % CI = 1.607~5.090,P < 0.001);KIR3DL1 rs35974949位点基因多态性与HCV慢性化以及KIR3DL1基因rs35656676位点基因多态性与HCV易感性和慢性化均无相关性(均P > 0.05)。
      结论  KIR3DL1 rs35974949位点基因多态性与HCV易感性有关。

     

    Abstract:
      Objective  To explore correlations of single nucleotide polymorphism (SNP) at KIR3DL1 rs35974949 and rs35656676 with the susceptibility and chronicity of hepatitis C virus (HCV) infection and to provide clinical evidences for screening, diagnosis and individualized prevention of HCV infection.
      Methods  With cluster sampling from August 2008 to December 2015, we conducted face-to-face questionnaire interview, detections of HCV RNA, anti-HCV antibodies and other related serum indicators, and genotyping of KIR3DL1 r35974949 and rs35656676 with quantitative real-time PCR TaqMan assay among 2 537 people aged 18 – 79 years and at high risk of HCV infection but not ever having interferon and direct antiviral drug treatment, including 1 788 rural residents with paid blood donation history from 25 villages and 749 hemodialysis patients from 9 tertiary hospitals in Jiangsu province. According to detection results, the participants were then assigned into one of the three groups: uninfected control group (1 512 individuals) being seronegative for both anti-HCV antibodies and HCV RNA, spontaneous HCV clearance group (382) being seropositive for anti-HCV antibodies but seronegative for HCV RNA, and persistent HCV infection group (643) being seropositive for both anti-HCV antibodies and HCV RNA. Multivariate logistic regression models were used to analyze relationships between SNP at KIR3DL1 rs35974949 and rs35656676 and the susceptibility and chronicity of HCV infection.
      Results  The proportions of KIR3DL1 rs35974949 GG, GT and TT genotype carriers were 78.47%, 20.05% and 1.49% in control group; 76.64%, 19.16% and 4.20% in spontaneous clearance group; and 74.34%, 19.60% and 6.07% in persistent HCV infection group; while, those of KIR3DL1 rs35656676 CC, CG and GG genotype carriers were 31.32%, 50.60% and 18.08% in control group; 31.68%, 49.74% and 18.59% in spontaneous clearance group; and 31.78%, 50.47% and 17.76% in persistent HCV infection group, respectively. After adjusting for gender, age, alanine aminotransferase (ALT) abnormality, aspartate aminotransferase (AST) abnormality and route of HCV infection, unconditional multivariate logistic regression analysis demonstrated that the individuals carrying KIR3DL1 rs35974949 TT genotype were more likely to have an increased HCV susceptibility (codominant model: adjusted odds ratio aOR = 2.802, 95% confidence interval 95% CI: 1.571 – 4.998, P < 0.001; recessive genetic model: aOR = 2.860, 95% CI: 1.607 – 5.090, P < 0.001) compared with those carrying KIR3DL1 rs35974949 GG/GT genotype. However, no significant association of KIR3DL1 rs35974949 genotype with HCV chronicity was derived. Furthermore, no significant associations of KIR3DL1 rs35656676 polymorphism with HCV susceptibility and chronicity were observed.
      Conclusion  Single nucleotide polymorphism at KIR3DL1 rs35974949 is associated with increased susceptibility of HCV infection in high risk populations.

     

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