Journal of Inflammation Research (Jan 2018)
Association between IL-18/18R gene polymorphisms and coronary artery disease: influence of IL-18/18R genetic variants on cytokine expression
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, Moscow, Russia; 2Federal Scientific Clinical Center for Specialized Types of Medical Assistance and Medical Technologies for the Federal Medical and Biological Agency, Moscow, Russia; 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 Purpose: The present study investigated the influence of IL-18/18R genetic variants on cytokine expression in patients with stable coronary artery disease (CAD). Materials and methods: The polymorphisms rs1946518, rs187238, rs326, rs1169288, and rs183130 were determined in patients with and without CAD. Circulating cytokine levels were measured immunologically. Results: The rs1946518-GG genotype shows higher IL-18 concentration in the group with CAD, but still not significant. The TG genotype from rs1946518 in carriers with CAD showed a significant decrease in relation to the pro-inflammatory cytokines IL-6, IL-8, and IL-18. The decreases of IL-6 and IL-8 were also specific for rs187238 CAD carriers with the GC genotype. The CAD carriers with the AA genotype from rs326 in the IL-18R gene showed significant increase in IL-8 and IL-18 in comparison with those without CAD. Regarding rs1169288 from the IL-18R gene, IL-8 showed a T allele-dependent increase. In the last rs183130 polymorphism of the IL-18R gene, the pro-inflammatory onset showed a C allele-dependent disease-associated decrease in IL-8 CC and IL-6 CT carriers. In contrast, the CAD CT carriers in relation to IL-8 showed significant increase. Conclusions: Most of the IL-18/18R single-nucleotide polymorphisms were mainly associated with pro-inflammatory cytokines. It is surmised that these associations between some pro-inflammatory cytokines (mainly IL-8) and some IL-18R genotypes in the subjects with CAD from this study are most likely based on inflammatory-induced upregulation of IL-18R expression. Keywords: Russian patients, inflammation, gene polymorphisms, IL-18/IL-18R genetic variants, inflammation, cytokines
