Interleukin-6 receptor Asp358Ala gene polymorphism is associated with plasma C-reactive protein levels and severity of aortic valve stenosis

Abstract

Interleukin-6 receptor (IL-6R) gene Asp358Ala (A>C, rs2228145) polymorphism has been associated with lower circulating inflammation biomarkers in coronary artery disease (CAD), such as C-reactive protein (CRP) or fibrinogen, but its role in the pathogenesis of aortic valve stenosis (AS) remains unknown. Since the pathogenesis of AS and atherosclerosis shares several similarities, we tested the hypothesis that IL-6R Asp358Ala polymorphism is associated with the severity of AS. A total of 284 AS patients aged 64.3±11.1 years were studied, in whom IL-6R polymorphism was determined by TaqMan genotyping. The genotype distribution was as follows: AA-43.7% (n=124); AC-37.0% (n=105); and CC-19.4% (n=55). For every copy of C allele inherited, mean concentration of CRP was reduced by 22% (95% CI 13.8-30.4; p<0.0001). Carriers of the C allele compared to the AA homozygotes were also characterized by lower mean and maximal transvalvular gradients [44.8 (30.5-60.0) vs. 52.7 (40.5-69.0) mmHg, p=0.0005; and 78.1±26.5 vs. 87.3±27.6 mmHg; p=0.008, respectively], and larger aortic valve area [0.8 (0.6-1.0) vs. 0.7 (0.5-0.9) cm2, p=0.005]. Our study is the first to show that the presence of the IL-6R 358Ala allele in AS patients is associated with attenuated systemic inflammatory state and less severe AS.