Interleukin-1 receptor antagonist gene polymorphism and coronary artery disease
Interleukin-1 receptor antagonist gene polymorphism and coronary artery disease
复制标题
DOI：
10.1161/01.cir.99.7.861
复制
发表时间：
1999-02-23
期刊：
影响因子：
37.8
通讯作者：
Crossman, DC
中科院分区：
文献类型：
--
作者：
Francis, SE;Camp, NJ;Crossman, DC
背景-细胞因子基因变异在炎症病理中起重要作用。对健康献血员、冠状动脉造影正常的患者(患者对照组)、单支冠状动脉疾病患者和多支冠状动脉疾病患者的IL-1簇基因[IL-1(-889)，IL-1B(-511)，IL-1B(+3953)，IL-1RN内含子2VNTR]和组织坏死因子-α基因[TNFA(-308)]的等位基因频率进行了检测。和328个MVD。在350：57的SVD、191个MVD和102个对照受试者的独立人群(伦敦)中测试了显著的相关性。谢菲尔德患者对照组IL-1RN*2频率与827例健康对照组相同。IL-1RN*2在Shefffield SVD患者中高表达(34%比23%)，在SVD人群中IL-1RN*2纯合子(X_1(2)携带者=8.490，1 df，P=0.0036)。这种影响在伦敦人群中是存在的，尽管不是很明显(P=0.0603)。对谢菲尔德和伦敦的IL-1RN SVD基因数据进行的趋势汇总检验显示，*2与*2显著相关(P=0.0024)。在谢菲尔德或伦敦MVD人群中，未观察到TL-1RN基因的显著影响。对TL-1RN的SVD型和MVD型进行了基因分布分析，结果显示TL1RN的SVD型和MVD型分布有非常显著的趋势(P=0.0007)。结论IL-1RN*2与SVD显著相关。SVD和MVD之间的遗传关联也明显不同。
Background-Cytokine gene variations are contributory factors in inflammatory pathology. Allele frequencies of interleukin (IL)-1 cluster genes [IL-1A(-889), IL-1B(-511), IL-1B(+3953), IL-1RN Intron 2 VNTR] and tissue necrosis factor (TNF)-alpha gene [TNFA(-308)] were measured in healthy blood donors (healthy control subjects), patients with angiographically normal coronary arteries (patient control subjects), single-vessel coronary disease (SVD), and those with multivessel coronary disease (MVD).Methods and Results-Five hundred fifty-six patients attending for coronary angiography in Sheffield were studied: 130 patient control subjects, 98 SVD, and 328 MVD. Significant associations were tested in an independent population (London) of 350: 57 SVD, 191 MVD, and 102 control subjects. IL-1RN*2 frequency in Sheffield patient control subjects was the same as in 827 healthy control subjects. IL-1RN*2 was significantly overrepresented in Sheffield SVD patients (34% vs 23% in patient control subjects); IL-1RN*2 homozygotes in the SVD population (chi(2) carriage=8.490, 1 df, P=0.0036). This effect was present though not quite significant in the London population (P=0.0603). A summary trend test of the IL-1RN SVD genotype data for Sheffield and London showed a significant association with *2 (P=0.0024). No significant effect of genotype at TL-1RN was observed in the Sheffield or London MVD populations. Genotype distribution analysis comparing the SVD and MVD populations at TL-1RN showed a highly significant trend (P=0.0007) with the use of pooled data. No significant associations were seen for the other polymorphisms.Conclusions-IL-1RN*2 was significantly associated with SVD. A difference in genetic association between SVD and MVD was also apparent.