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TNF-α polymorphisms and coronary artery disease: Association study in the Korean population

机译：TNF-α多态性与冠状动脉疾病：韩国人群的关联研究

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摘要

Coronary artery disease (CAD) results from atherosclerosis, a chronic inflammatory disease mediated in part by proinflammatory cytokines, particularly tumor necrosis factor-α (TNF-α), which is expressed by atherosclerotic plaques. In this study, we investigated whether TNF-α gene promoter polymorphisms affect the incidence of CAD in Koreans by genotyping. 404 Control subjects and 197 patients who previously received a coronary artery stent for the G/A, C/T, and C/A polymorphisms at position -238, -857 and -863, respectively. The G/G, G/A and A/A genotypes at position -238 occurred in 85.8%, 14.2% and 0% CAD patients and 91.8%, 7.9% and 0.3% control subjects, respectively. The G/A polymorphisms at position -238 were significantly associated with CAD when assuming a dominant model of inheritance (OR = 1.87; 95% CI = 1.10-3.20; P=0.02), and A allele carriers had a significantly increased risk of developing CAD relative to the G allele (OR = 1.74; 95% CI = 1.04-2.92; P=0.03). However, the polymorphisms at positions -857 and -863 were not associated with CAD. Haplotype-based analysis revealed the CAD and control groups differed significantly in the frequencies of haplotype ACC at positions -238, -857 and -863 (OR = 1.77; 95% CI = 1.05-2.98; P=0.03). This was confirmed by multivariate analysis after adjusting body mass index and the presence of diabetes and hypertension (OR = 2.06; 95% CI = 1.15-3.68; P=0.015). Thus, the -238A allele of TNF-α is associated with an increased risk of CAD and could be used as predictor for CAD in Koreans. Further studies are needed to elucidate the clinical implications of these findings.
机译：冠状动脉疾病（CAD）是由动脉粥样硬化引起的，动脉粥样硬化是部分由促炎细胞因子尤其是肿瘤坏死因子-α（TNF-α）介导的慢性炎性疾病，它由动脉粥样硬化斑块表达。在这项研究中，我们调查了TNF-α基因启动子多态性是否通过基因分型影响韩国人CAD的发病率。 404例对照受试者和197例先前在-238，-857和-863位置分别接受了G / A，C / T和C / A多态性的冠状动脉支架的患者。 -238位的G / G，G / A和A / A基因型分别发生在85.8％，14.2％和0％的CAD患者以及91.8％，7.9％和0.3％的对照患者中。当假定遗传为显性遗传模型时，-238位的G / A多态性与CAD显着相关（OR = 1.87; 95％CI = 1.10-3.20; P = 0.02），并且等位基因携带者的发生风险显着增加相对于G等位基因的CAD（OR = 1.74; 95％CI = 1.04-2.92; P = 0.03）。但是，-857和-863位的多态性与CAD无关。基于单倍型的分析显示，CAD和对照组在-238，-857和-863位置的单倍型ACC频率存在显着差异（OR = 1.77; 95％CI = 1.05-2.98; P = 0.03）。调整体重指数以及糖尿病和高血压的存在后，通过多元分析证实了这一点（OR = 2.06; 95％CI = 1.15-3.68; P = 0.015）。因此，TNF-α的-238A等位基因与CAD风险增加有关，可以用作韩国人CAD的预测因子。需要进一步的研究来阐明这些发现的临床意义。

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