Association of interleukin-6 gene polymorphism rs1800795, interleukin-6 level with presence and severity of coronary atherosclerosis

Background. Coronary atherosclerosis, driven by inflammation, remains a leading cause of mortality. Interleukin-6 (IL-6) is a key proinflammatory cytokine. The rs1800795 polymorphism of the IL6 gene may influence IL-6 levels; however, data on its association with atherosclerosis are conflicting, particularly for the Russian population.

Objective: to comprehensively assess the association of the gene IL6 rs1800795 polymorphism and plasma IL-6 levels with the presence and severity of coronary atherosclerosis in patients from the Russian population.

Methods. The study included 476 patients undergoing coronary angiography. Groups were formed: with atherosclerosis (stenosis ≥50%, n=384) and without (n=92). The rs1800795 polymorphism was genotyped using real-time PCR, and IL-6 levels were determined by enzyme-linked immunosorbent assay (ELISA). Atherosclerosis severity was assessed by the number of affected arteries and the GensiniScore.

Results. IL-6 levels were significantly higher in the atherosclerosis group (3.56 vs. 2.08 pg/mL; p=0.008) and were associated with its presence after adjustment for atherosclerosis risk factors and statin use (OR=4.26; 95% CI: 1.22–14.81). IL-6 concentration significantly increased with a greater number of affected arteries (p=0.02) and showed a weak correlation with the GensiniScore (r=0.15, p=0.04). Carriers of the C/C genotype had significantly lower IL-6 levels (3.76 vs. 5.26 pg/mL, p=0.04). The C/C genotype was associated with a lower likelihood of atherosclerosis in the univariate analysis (OR=0.55; 95% CI: 0.32–0.95) but not after multivariate adjustment (OR=0.57; 95% CI: 0.31–1.05).

Conclusions. Elevated IL-6 level is an independent risk factor for the presence and severity of coronary atherosclerosis. The C/C genotype of rs1800795 is associated with reduced IL-6 levels and demonstrates a trend toward a protective effect; however, this association is not independent of traditional risk factors.

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