Association between interleukin-6/6R gene polymorphisms and coronary artery disease in Russian population: influence of interleukin-6/6R gene polymorphisms on inflammatory markers

Abstract

Vadim Mitrokhin,1 Alexey Nikitin,2 Olga Brovkina,2 Dmitry Khodyrev,2 Alexander Zotov,2 Nikita Vachrushev,1 Dmitry Dragunov,3 Andrey Shim,1 Mitko Mladenov,1,4 Andre Kamkin1 1Department of Fundamental and Applied Physiology, Russian National Research Medical University, 2Federal Scientific Clinical Center for Specialized Types of Medical Assistance and Medical Technologies for the Federal Medical and Biological Agency, 3Scientific Research Institute of Healthcare Organization and Medical Management, Moscow, Russia; 4Faculty of Natural Sciences and Mathematics, Institute of Biology, Ss. Cyril and Methodius University, Skopje, Macedonia Abstract: This study determined the genotype effects of interleukin (IL)-6/IL-6R single nucleotide polymorphisms (SNPs) on circulating levels of different cytokines in healthy and coronary artery disease (CAD) patients with different allele frequencies. In the control patients, rs1800795 showed significant differences in IL-18 concentrations between CC and CG and CC and GG genotypes (P=0.003 and 0.004, respectively). Furthermore, circulatory IL-1β was significantly different between GC and GG genotypes from the same SNP (P=0.038). In the diseased patients, significance was determined only for IL-2 (P=0.021) between the C and G homozygote allele carriers of rs1800795. The diseased GC and GG genotype carriers were statistically different for IL-2 (P=0.049) from the rs1800796 and for IL-4 (P=0.049) from the rs2228044. IL-4 was also statistically significant between the GC and CC genotypes from the rs2228043 of the IL-6R gene (P=0.025). The last combination of genotypes in the same gene for the same SNP was statistically significant for IL-10 (P=0.036). According to the logistic regression, only gender (odds ratio [OR] =2.43) and triglycerides (OR =1.98) could be taken as determinants of CAD, while examined SNPs genotypes were not identified as risk factors for CAD. In general, the IL-6 polymorphism genotypes were mainly associated with inflammatory cytokines, while the IL-6R polymorphism genotypes were associated with anti-inflammatory cytokines. Keywords: IL-6/IL-6R gene polymorphisms, coronary artery disease, cytokines, inflammation

Keywords

• IL-6/IL-6R gene polymorphisms
• Coronary artery disease
• Cytokines
• Inflammation;