Association of interleukin gene polymorphisms with coronary artery disease severity

Aim The present study was aimed to investigate the association between genetic variants interleukin-1β (IL-1β) rs16944 (A/G), rs1143623 (C/G) and rs4848306 (A/G), IL-6 rs1800796 (G/C), and IL-6R rs4845625 (T/C) and the severity in coronary artery disease (CAD). Methods This was a secondary analysis based on a large-scale (n=10724), observational, single-center, prospective cohort of patients with CAD who underwent percutaneous coronary intervention (PCI). Genotyping of five gene polymorphisms was performed using the targeted capture technology independently developed by a certain company. The primary endpoint was the coronary artery disease severity, which was graded according to the SYNTAX score (SS). An SS below 22 was considered to indicate low severity, while an SS of 22 or above indicated intermediate-high severity. Multivariate logistic regression models were employed to analyze the association of the selected gene polymorphisms with the coronary artery disease severity. The odd ratios (OR) and 95% confidence intervals (CI) were calculated under various genetic models, including dominant, recessive, homozygous, heterozygous, and allelic model. Results A total of 4080 patients who had available DNA samples and passed DNA genotyping were included in the current analysis, after excluding patients with previous coronary artery bypass grafting (CABG) and without records of SS. By multivariate logistic regression analysis, we found that the GG genotype of IL-1β rs16944 (A/G) was significantly associated with low severity, with OR (95% CI) of 0.72 (0.57-0.91). In addition, the CC genotype and the C allele of IL-1β rs1143623 (C/G) was also significantly associated with low severity (GG/GC vs. CC, OR:1.34, 95% CI: 1.08-1.66; GG vs. CC, OR: 1.36, 95% CI: 1.01-1.82; GC vs. CC, OR: 1.33, 95% CI: 1.07-1.67; G vs. C, OR: 1.19, 95% CI: 1.03-1.37). Meanwhile, the AA genotype of IL-1β rs4848306 (A/G) was significantly associated with low severity, with OR (95% CI) of 0.71 (0.55-0.91). However, IL-6 rs1800796 (G/C) and IL-6R rs4845625 (T/C) did not significantly associate with the coronary artery disease severity. Conclusion Our study suggests that the IL-1β rs16944 (A/G), rs1143623 (C/G) and rs4848306 (A/G) polymorphisms might be involved in the development of CAD, indicating that the detection of IL-1β gene polymorphism could contribute to the early identification of CAD patients at high risk.