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.
Liu
Wenwei
W
Department of Cardiology, Xiangfan Central Hospital, Xiangfan, Hubei, China. liuwenwei@medmail.com.cn
Tang
Qizhu
Q
Jiang
Hua
H
Ding
Xiangwu
X
Liu
Yongsheng
Y
Zhu
Rui
R
Tang
Yongqian
Y
Li
Bin
B
Wei
Min
M
D000483:Alleles; D017023:Coronary Angiography / Q000379:methods*; D003324:Coronary Artery Disease / Q000097:blood / Q000000981:diagnostic imaging / Q000235:genetics*; D004247:DNA / Q000235:genetics*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D020382:Interleukin-18 / Q000097:blood / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011379:Prognosis; D011401:Promoter Regions, Genetic; D012189:Retrospective Studies
D020382:Interleukin-18; D004247:DNA