Promoter Polymorphism of Interleukin18 in Angiographically Proven Coronary Artery Disease

Department of Cardiology, Xiangfan Central Hospital, Xiangfan, Hubei, China.
Angiology (Impact Factor: 2.97). 04/2009; 60(2):180-185. DOI: 10.1177/0003319708319939


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.

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    • "In patients experiencing IS, peripheral blood levels of IL-18 have been found to be significantly higher compared to healthy individuals (9,10). Specifically, an SNP in the IL-18 promoter (designated -607C/A) has been associated with the development of cardiovascular disease (11,12), which can include vascular endothelial damage and formation of atherosclerosis, processes that can induce stroke. This polymorphism affects the expression and activity of IL-18 (13-15), thereby offering a potential mechanistic basis leading to increased susceptibility to cardiovascular disease. "
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    ABSTRACT: Single nucleotide polymorphisms in the promoter region of interleukin-18 (IL-18), an inflammatory cytokine, have been linked to susceptibility to many diseases, including cancer and immune dysfunction. Here, we explored the potential association between the IL-18 -607C/A (rs1946518) promoter region polymorphism and susceptibility to ischemic stroke (IS). This locus was amplified from peripheral blood samples of 386 IS patients (cases) and 364 healthy individuals (controls) by the polymerase chain reaction with sequence-specific primers. Significant differences were observed by the χ2 test in the -607C/A (rs1946518) genotype and allele frequencies between cases and controls (P < 0.05). Furthermore, after excluding for age, gender, smoking status, and hypertension, logistic regression indicated that IS susceptibility of -607C carriers increased 1.6 times (OR = 1.601, 95%CI = 1.148-2.233, P = 0.006) compared to -607A carriers. Additionally, similar increases in IS risk were noted for male patients or patients less than 65 years old. In conclusion, IL-18 -607C/A (rs1946518) promoter polymorphism is associated with IS susceptibility, and the C allele may confer increased IS risk.
    Full-text · Article · May 2013 · Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas / Sociedade Brasileira de Biofisica ... [et al.]
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    • "Of interest also is the observation that neutralization of endogenous IL-18 allows tumors to grow more rapidly indicating that in this model IL-18 is important for tumor immune surveillance (Fig. 1 C). In line with this observation, single nucleotide polymorphisms (SNPs) within the human IL-18 gene that are associated with lower promoter activity and lower gene expression [41], may influence susceptibility to certain cancers including prostate cancer [42], nasopharyngeal cancer [43] and esophageal squamous cell carcinoma [44]. Moreover, human prostate cancer cell lines and clinical PCa specimens are reported to express IL-18 receptor α [45] and IL-18 expression was associated with better patient outcome. "
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    No preview · Conference Paper · Dec 2004
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