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经血管造影证实的冠状动脉疾病中白细胞介素-18启动子多态性

Promoter polymorphism of interleukin-18 in angiographically proven coronary artery disease.

作者信息

Liu Wenwei, Tang Qizhu, Jiang Hua, Ding Xiangwu, Liu Yongsheng, Zhu Rui, Tang Yongqian, Li Bin, Wei Min

机构信息

Department of Cardiology, Xiangfan Central Hospital, Xiangfan, Hubei, China.

出版信息

Angiology. 2009 Apr-May;60(2):180-5. doi: 10.1177/0003319708319939. Epub 2008 Jul 3.

DOI:10.1177/0003319708319939
PMID:18599493
Abstract

Interleukin 18 (IL-18) is a pro-atherogenic cytokine associated with the occurrence of various cardiac complications. The IL-18 gene has a functional -137 G/C polymorphism (rs187238) in the promoter region. Using the ligase detection reaction-polymerase chain reaction, we genotyped a cohort of patients in Chinese Han population in Xiangfan region. Case patients of coronary artery disease and control patients were identified by coronary angiography. The plasma IL-18 concentrations were measured by ELISA. A significant increase of G allele or GG-genotype was observed in 241 case patients compared to 145 control individuals (frequency of G allele = 0.90 vs 0.83, p=0.004; frequency of GG-genotype = 0.81 vs 0.68, p = 0.005). In case patients, G allele carriers in multi-vessel disease patients had a higher occurrence rate when compared to single-vessel disease patients, but no significant difference was detected (frequency of G allele = 0.92 vs 0.88, p=0.107; frequency of GG-genotype = 0.84 vs 0.75, p = 0.089). IL-18 protein concentration of the -137GG genotype was much higher than concentration of the CG and CC genotype (case patients: 229.1+/-131.5 vs 122.7+/-73.6 pg/ml, P < 0.001; control patients: 65.9+/-31.6 vs 42.4+/-19.5 pg/ml, P < 0.001). To conclude, IL-18 promoter -137G/C polymorphism influences IL-18 levels and the occurrence of coronary artery disease, suggesting that IL-18 is causally involved in the development of atherosclerosis.

摘要

白细胞介素18(IL-18)是一种促动脉粥样硬化细胞因子,与多种心脏并发症的发生有关。IL-18基因在启动子区域存在功能性-137G/C多态性(rs187238)。我们采用连接酶检测反应-聚合酶链反应对襄樊地区中国汉族人群的一组患者进行基因分型。通过冠状动脉造影确定冠心病患者和对照患者。采用酶联免疫吸附测定法(ELISA)检测血浆IL-18浓度。与145名对照个体相比,241例患者中观察到G等位基因或GG基因型显著增加(G等位基因频率=0.90对0.83,p=0.004;GG基因型频率=0.81对0.68,p=0.005)。在患者中,多支血管病变患者的G等位基因携带者发生率高于单支血管病变患者,但差异无统计学意义(G等位基因频率=0.92对0.88,p=0.107;GG基因型频率=0.84对0.75,p=0.089)。-137GG基因型的IL-18蛋白浓度远高于CG和CC基因型(患者:229.1±131.5对122.7±73.6 pg/ml,P<0.001;对照患者:65.9±31.6对42.4±19.5 pg/ml,P<0.001)。总之,IL-18启动子-137G/C多态性影响IL-18水平和冠状动脉疾病的发生,提示IL-18与动脉粥样硬化的发生存在因果关系。

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