Interleukin-18 promoter polymorphism associates with the occurrence of sudden cardiac death among Caucasian males: The Helsinki Sudden Death Study

Objective The increased plasma concentrations of pro-atherogenic and cardiomyocyte hypertrophic cytokine interleukin 18 (IL-18) predict mortality in patients with coronary heart disease (CHD) in addition to predicting the outcome of heart failure. The IL-18 gene has a functional −137 G/C polymorphism (rs187238) in the promoter region. The C allele carriage is associated with attenuated IL-18 production. The effect of IL-18 genotype on SCD is unknown. We studied the association of the IL-18 gene −137 G/C polymorphism with the occurrence of sudden cardiac death (SCD). Methods Using the TaqMan 5′ nuclease assay, we genotyped two independent consecutive and prospective autopsy series which were included in the Helsinki Sudden Death Study. Results Of the 663 men, 359 (54.1%) had the wild-type GG-genotype, 261 (39.4%) were heterozygotes (CG) and 43 (6.5%) were CC homozygotes. Compared to the GG homozygotes, the C allele carriers (i.e. subjects having CC or CG genotypes) had a lower adjusted risk for SCD from any cause (odds ratio [OR] 0.49; 95% confidence interval [CI], 0.31–0.77, p = 0.002), for SCD due to CHD (OR 0.51; 95% CI, 0.32–0.82, p = 0.005), and for SCD caused by non-coronary heart diseases (OR 0.34; 95% CI 0.13–0.90, p = 0.030). Conclusion IL-18 promoter −137 G/C polymorphism, which regulates the expression of IL-18, is an important predictor of SCD from any cause as well as SCD in patients with and without underlying CHD.