Promoter Polymorphism of Interleukin-18 in Angiographically Proven Coronary Artery Disease

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.