Mitrokhin Vadim, Nikitin Alexey, Brovkina Olga, Khodyrev Dmitry, Zotov Alexander, Vachrushev Nikita, Dragunov Dmitry, Shim Andrey, Mladenov Mitko, Kamkin Andre
Department of Fundamental and Applied Physiology, Russian National Research Medical University, Moscow, Russia.
Federal Scientific Clinical Center for Specialized Types of Medical Assistance and Medical Technologies for the Federal Medical and Biological Agency, Moscow, Russia.
J Inflamm Res. 2018 Jan 18;11:1-9. doi: 10.2147/JIR.S153370. eCollection 2018.
The present study investigated the influence of IL-18/18R genetic variants on cytokine expression in patients with stable coronary artery disease (CAD).
The polymorphisms rs1946518, rs187238, rs326, rs1169288, and rs183130 were determined in patients with and without CAD. Circulating cytokine levels were measured immunologically.
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.
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.
本研究调查白细胞介素-18（IL-18）/18受体（18R）基因变异对稳定型冠状动脉疾病（CAD）患者细胞因子表达的影响。
测定了CAD患者和非CAD患者的rs1946518、rs187238、rs326、rs1169288和rs183130基因多态性。采用免疫学方法检测循环细胞因子水平。
rs1946518-GG基因型在CAD组中IL-18浓度较高，但仍无统计学意义。CAD携带者中rs1946518的TG基因型与促炎细胞因子IL-6、IL-8和IL-18相比显著降低。IL-6和IL-8的降低也见于rs187238的GC基因型CAD携带者。IL-18R基因rs326的AA基因型CAD携带者与非CAD者相比，IL-8和IL-18显著升高。关于IL-18R基因的rs1169288，IL-8呈T等位基因依赖性升高。在IL-18R基因的最后一个rs183130多态性中，促炎发作在IL-8 CC和IL-6 CT携带者中呈C等位基因依赖性疾病相关降低。相反，CAD CT携带者的IL-8显著升高。
大多数IL-18/18R单核苷酸多态性主要与促炎细胞因子相关。推测本研究中CAD患者某些促炎细胞因子（主要是IL-8）与某些IL-18R基因型之间的这些关联很可能基于炎症诱导的IL-18R表达上调。
