Regulatory polymorphisms in the IL‐10 gene promoter and HBV‐related acute liver failure in the Chinese population
Regulatory polymorphisms in the IL‐10 gene promoter and HBV‐related acute liver failure in the Chinese population
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DOI：
10.1111/j.1365-2893.2009.01139.x
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发表时间：
2009-11
影响因子：
2.5
通讯作者：
Ze-hui Yan;W. Tan;Wenli Zhao;Y. Dan;Xiao-Hong Wang;Qing Mao;Yuming Wang;Guohong Deng
中科院分区：
文献类型：
--
作者：
Ze-hui Yan;W. Tan;Wenli Zhao;Y. Dan;Xiao-Hong Wang;Qing Mao;Yuming Wang;Guohong Deng
摘要最近的报告表明，高水平的白细胞介素10（IL-10）有助于单核细胞麻痹和急性肝功能衰竭（ALF）的临床结果不佳。IL-10启动子区的多态性影响IL-10的产生并赋予对炎性疾病的易感性。本研究的目的是确定中国人群中IL-10基因启动子的三种多态性（A-1082 G、T-819 C、A-592 C）与B型肝炎病毒（HBV）相关ALF易感性的可能关联。在414名无关健康献血者、367名无症状HBV携带者和345名HBV相关ALF患者中对IL-10基因启动子多态性进行基因分型。进行功能分析以验证相关遗传变异的生物学意义。HBV相关ALF患者中IL-10− 592 C和− 819 C的等位基因频率显著高于献血员和无症状HBV携带者。Logistic回归分析和校正年龄和性别后的分层分析表明，A-592 C和T-819 C多态性与HBV相关ALF的易感性相关（P = 6.9 × 10−7），IL-10基因启动子中的-1082 A-819 C-592 C单倍型与HBV携带者对ALF的易感性增加相关（显性模型，P = 0.0002，比值比= 1.60，95%CI 1.25-2.07）。功能分析表明，A-592 C多态性是一个核蛋白结合位点，疾病易感的− 592 C等位基因比− 592 A等位基因具有更高的转录活性。这项研究强调了IL-10在人群水平上HBV相关ALF病理生理学中的重要性。
Summary. Recent reports indicated that high levels of interleukin 10 (IL‐10) contribute to the monocytes paralysis and poor clinical outcome in acute liver failure (ALF). Polymorphisms in the promoter region of IL‐10 affect IL‐10 production and confer susceptibility to inflammatory diseases. The aim of this study was to determine the possible association of the three polymorphisms (A‐1082G, T‐819C, A‐592C) in the IL‐10 gene promoter with the susceptibility to hepatitis B virus (HBV)‐related ALF in a Chinese population. The IL‐10 gene promoter polymorphisms were genotyped in 414 unrelated healthy blood donors, 367 asymptomatic HBV carriers and 345 HBV‐related ALF patients. Functional analyses were conducted to verify the biological significances of the associated genetic variations. The allele frequencies of IL‐10−592C and −819C were significantly higher in HBV‐related ALF patients than in blood donors and asymptomatic HBV carriers. Logistic regression analysis and stratification analysis with adjustment for age and sex indicated that the polymorphisms of A‐592C and T‐819C were associated with susceptibility to HBV‐related ALF (P = 6.9 × 10−7), and the ‐1082A‐819C‐592C haplotype in the IL‐10 gene promoter were associated with an increased susceptibility to ALF in HBV carriers (dominant model, P = 0.0002, odds ratio = 1.60, 95% CI 1.25–2.07). Functional analyses showed that the A‐592C polymorphism is a nuclear proteins binding site, and the disease susceptible −592C allele had a higher transcription activity compared with −592A allele. This study emphasizes the importance of IL‐10 in the pathophysiology of HBV‐related ALF on the population level.