Chronic inflammation mediated by cytokines is central to the pathogenesis of coronary artery disease (CAD). This exploratory study aimed to investigate potential associations between functional gene variations of the cytokines interleukin 18 (IL-18) and interleukin 8 (IL-8) and the CAD susceptibility within a specific regional cohort, while accounting for common clinical comorbidities. Genotype distributions of IL-18 (−607 C/A, −137 G/C) and IL-8 (+781 C/T) were analyzed in a cohort of 102 patients with angiographically confirmed CAD and 102 healthy controls. Genotyping was performed using PCR, allele-specific PCR, and RFLP techniques. Multivariate logistic regression was utilized to assess potential independent associations, adjusting for age and traditional clinical risk factors. In this specific cohort, after adjusting for age, hypertension, diabetes, cholesterol, family history, and smoking, the IL-18 (−137 G/C) CC genotype was observed more frequently in CAD patients (adjusted odds ratio AOR = 6.15, 95% CI = 2.10–18.05, p = 0.001). An exploratory analysis of genotype combinations suggested that the IL-18 (−607/−137) CA-CC profile may be linked to an increased risk (AOR = 3.65, p = 0.028), while tentative protective trends were noted for certain IL-18/IL-8 combinations. Notably, a significant deviation from a Hardy–Weinberg equilibrium (HWE) was observed in the control group for the IL-18 loci, which represents a substantial methodological limitation that may influence these risk estimates. Our preliminary findings suggest that specific IL-18 and IL-8 variations may contribute to CAD susceptibility independently of traditional risk factors in the studied population. However, given the modest sample size and the observed HWE deviation, these associations should be regarded as suggestive rather than definitive. While these genetic variations underscore the importance of cytokine pathways in cardiovascular research, they do not currently support clinical implementation for risk stratification. Large-scale, multi-center prospective studies are necessary to validate these preliminary signals and evaluate their long-term scientific utility.
Ay et al. (Tue,) studied this question.