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.
Federal Scientific Clinical Center for Specialized Types of Medical Assistance and Medical Technologies for the Federal Medical and Biological Agency.
J Inflamm Res. 2017 Oct 3;10:151-160. doi: 10.2147/JIR.S141682. eCollection 2017.
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 (=0.003 and 0.004, respectively). Furthermore, circulatory IL-1β was significantly different between GC and GG genotypes from the same SNP (=0.038). In the diseased patients, significance was determined only for IL-2 (=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 (=0.049) from the rs1800796 and for IL-4 (=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 (=0.025). The last combination of genotypes in the same gene for the same SNP was statistically significant for IL-10 (=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.
本研究确定了白细胞介素(IL)-6/IL-6受体单核苷酸多态性(SNP)在不同等位基因频率的健康和冠状动脉疾病(CAD)患者中对不同细胞因子循环水平的基因型效应。在对照患者中,rs1800795在CC与CG以及CC与GG基因型之间的IL-18浓度显示出显著差异(分别为=0.003和0.004)。此外,来自同一SNP的GC与GG基因型之间的循环IL-1β有显著差异(=0.038)。在患病患者中,仅rs1800795的C和G纯合子等位基因携带者之间的IL-2有显著性差异(=0.021)。患病的GC和GG基因型携带者在rs1800796的IL-2方面(=0.049)以及rs2228044的IL-4方面(=0.049)存在统计学差异。IL-6受体基因的rs2228043的GC与CC基因型之间的IL-4也具有统计学显著性(=0.025)。同一基因中同一SNP的最后一组基因型组合在IL-10方面具有统计学显著性(=0.036)。根据逻辑回归分析,只有性别(优势比[OR]=2.43)和甘油三酯(OR =1.98)可被视为CAD的决定因素,而所检测的SNP基因型未被确定为CAD的危险因素。总体而言,IL-6多态性基因型主要与炎性细胞因子相关,而IL-6受体多态性基因型与抗炎细胞因子相关。