Interleukin-6 rs1800796 G/C polymorphism is associated with poor clinical outcomes in patients with coronary artery disease

Background Interleukin-6 (IL-6) and IL-6 receptor (IL-6R) gene polymorphisms play an important role in the initiation of coronary artery disease (CAD). However, their link to the poor clinical outcomes of CAD patients remains unknown. The present study was designed to investigate the association between IL-6 and IL-6R gene single nucleotide polymorphisms (SNPs) and long-term major adverse cardiac and cerebrovascular events (MACCE) based on a large-scale (n=10724), observational, single-center, prospective cohort of patients with CAD who underwent percutaneous coronary intervention (PCI). Methods Of 10724, 4304 patients available DNA samples and successfully completed DNA genotyping entered the final analysis. All 4304 subjects were genotyped for IL-6 rs1800796 (G/C), and IL-6R rs4845625 (T/C). The primary endpoint was MACCE, which consists of all-cause death, myocardial infarction, revascularization, and stroke. Univariate and multivariate Cox regression models were employed to analyze the association of the selected SNPs with the risk of MACCE. The hazard ratios (HR) and 95% confidence intervals (CI) were calculated under various genetic models, including dominant, recessive, homozygous, heterozygous, and allelic model. Results After a median follow-up of 5 years, 934 (21.7% ) MACCE occurred. All SNPs conformed to Hardy-Weinberg equilibrium in patients with and without MACCE (P>0.05) (Table 1 & Table 2). Multivariate Cox regression revealed that when the IL-6 rs1800796 GG homozygote genotype was used as the reference group, the GC/CC or GC genotypes were associated with lower likelihood of 5-year MACCE (GC+CC vs. GG, HR=0.810; 95% CI=0.661-0.993, p=0.043; GC vs. GG, HR: 0.823; 95% CI=0.680-0.997, p=0.047) (Table 3). No significant association between IL-6R rs4845625 (T/C) and the risk of MACCE. Conclusion The present study reported for the first time that the IL-6 rs1800796 (G/C) functional SNP was associated with risk of 5-year MACCE in patients with PCI, indicating that the detection of IL-6 gene polymorphism could contribute to the early identification of CAD patients at high risk.