Manginas Athanassios, Tsiavou Anastasia, Chaidaroglou Antigoni, Giamouzis Grigorios, Degiannis Dimitrios, Panagiotakos Demosthenis, Cokkinos Dennis V
Department of Cardiology, Onassis Cardiac Surgery Center, Athens, Greece.
Coron Artery Dis. 2008 Dec;19(8):575-82. doi: 10.1097/MCA.0b013e32831286e8.
Abundant evidence supports the central role of inflammatory cytokines in immune responses mediating the pathogenesis of atherosclerosis, coronary artery disease, and its complications, such as myocardial infarction and unstable angina.
We investigated the association of genetic polymorphisms of the inflammatory cytokines, IL-10, TGF-beta1, IFN-gamma, IL-6, and TNF-alpha with the clinical presentation of coronary artery disease in 26 patients with stable angina, 45 patients with unstable angina and 58 patients who had experienced nonfatal myocardial infarction. Genotyping was performed by the sequence-specific primer polymerase chain reaction method.
A significant difference in the frequencies of -174G/C IL-6 alleles was observed, with the low in-vitro producing -174*C allele predominating in patients with myocardial infarction, compared with stable angina and unstable angina patients, after the analysis of genotypes (P=0.024 and 0.022, respectively), phenotypes [P=0.0099, odds ratio (OR)=0.271, 95% confidence interval (CI)=0.1012-0.7292; P=0.03, OR=0.40, respectively] and haplotypes (P=0.007, OR=3.028, 95% CI=1.347-6.806; P=0.0096, OR=2.368, 95% CI=1.262-4.444; respectively). In addition, a predominance of the -1082ACC/ATA IL-10 genotype in the myocardial infarction group compared with the unstable angina group and the -874 A/A IFN-gamma genotype in the stable angina group compared with the unstable angina and the myocardial infarction group, was found. No significant differences in the distribution of genotypes, phenotypes and haplotypes in the three study groups, for the TNF-alpha-308 A/G and TGF-beta1-codon 25 G/C, codon 10 T/C polymorphisms were detected.
Our data provide evidence that the IL-6-174G/C polymorphism may be involved in the pathogenesis of coronary artery disease, contributing to genetic susceptibility for myocardial infarction.
大量证据支持炎性细胞因子在介导动脉粥样硬化、冠状动脉疾病及其并发症（如心肌梗死和不稳定型心绞痛）发病机制的免疫反应中起核心作用。
我们调查了炎性细胞因子白细胞介素-10（IL-10）、转化生长因子-β1（TGF-β1）、干扰素-γ（IFN-γ）、白细胞介素-6（IL-6）和肿瘤坏死因子-α（TNF-α）的基因多态性与26例稳定型心绞痛患者、45例不稳定型心绞痛患者和58例非致命性心肌梗死患者冠状动脉疾病临床表现之间的关联。采用序列特异性引物聚合酶链反应法进行基因分型。
在分析基因型（分别为P = 0.024和0.022）、表型[P = 0.0099，优势比（OR）= 0.271，95%置信区间（CI）= 0.1012 - 0.7292；分别为P = 0.03，OR = 0.40]和单倍型（P = 0.007，OR = 3.028，95% CI = 1.347 - 6.806；P = 0.0096，OR = 2.368，95% CI = 1.262 - 4.444；分别）后，观察到-174G/C IL-6等位基因频率存在显著差异，低体外产生的-174*C等位基因在心肌梗死患者中占主导，与稳定型心绞痛和不稳定型心绞痛患者相比。此外，发现心肌梗死组中-1082ACC/ATA IL-10基因型相较于不稳定型心绞痛组占优势，稳定型心绞痛组中-874 A/A IFN-γ基因型相较于不稳定型心绞痛组和心肌梗死组占优势。对于TNF-α - 308 A/G和TGF-β1 - 密码子25 G/C、密码子10 T/C多态性，在三个研究组的基因型、表型和单倍型分布中未检测到显著差异。
我们的数据提供了证据，表明IL-6 - 174G/C多态性可能参与冠状动脉疾病的发病机制，导致心肌梗死的遗传易感性。
