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白细胞介素-27基因多态性与墨西哥人群的早发性冠状动脉疾病及代谢参数相关:动脉粥样硬化疾病遗传学(GEA)墨西哥研究

Interleukin-27 polymorphisms are associated with premature coronary artery disease and metabolic parameters in the Mexican population: the genetics of atherosclerotic disease (GEA) Mexican study.

作者信息

Posadas-Sánchez Rosalinda, Pérez-Hernández Nonanzit, Rodríguez-Pérez José Manuel, Coral-Vázquez Ramón M, Roque-Ramírez Bladimir, Llorente Luis, Lima Guadalupe, Flores-Dominguez Carmina, Villarreal-Molina Teresa, Posadas-Romero Carlos, Vargas-Alarcón Gilberto

机构信息

Departamento de Endocrinología, Instituto Nacional de Cardiología Ignacio Chávez, Mexico D.F., México.

Departamento de Biología Molecular, Instituto Nacional de Cardiología Ignacio Chávez, Mexico D.F., México.

出版信息

Oncotarget. 2017 Mar 15;8(38):64459-64470. doi: 10.18632/oncotarget.16223. eCollection 2017 Sep 8.

Abstract

Several studies suggest an important role of Interleukin-27 in the development of atherosclerosis. The aim of this study was to establish whether the gene polymorphisms are associated with premature coronary artery disease and/or other cardiovascular risk factors. Four gene polymorphisms were selected and genotyped in 1162 premature coronary artery disease cases and 1107 controls. rs26528 and rs40837 alleles were significantly associated with a lower risk of premature coronary artery disease under different inheritance models (P = 0.046; P = 0.002; P = 0.007 for rs26528T; P = 0.008 and P = 0.031 for rs40837). The rs40837 allele was also associated with a lower risk of insulin resistance, in cases (P = 0.037) and controls (P = 0.008; P = 0.047; P = 0.014; P = 0.006), while the rs26528 allele was associated with a lower risk of insulin resistance only in the control group (P = 0.016; P = 0.021). Interleukin-27 plasma levels were measured in 450 controls and 450 cases, and were significantly higher in cases compared to controls (P = 0.004). However, Interleukin-27 plasma levels were not associated with polymorphisms. Luciferase assays showed that co-transfection of the rs40837 allele and miR-379-5p significantly decreased luciferase gene expression. Our study shows for the first time, that IL gene polymorphisms are associated with premature coronary artery disease and with some metabolic parameters. The rs40837 allele in presence of miR-379-5p significantly decreased luciferase gene expression.

摘要

多项研究表明白细胞介素-27在动脉粥样硬化发展过程中起重要作用。本研究的目的是确定基因多态性是否与早发性冠状动脉疾病和/或其他心血管危险因素相关。选取了四个基因多态性位点,并在1162例早发性冠状动脉疾病患者和1107例对照中进行基因分型。在不同遗传模型下,rs26528和rs40837等位基因与早发性冠状动脉疾病风险降低显著相关(rs26528T的P = 0.046;P = 0.002;P = 0.007;rs40837的P = 0.008和P = 0.031)。rs40837等位基因在患者(P = 0.037)和对照(P = 0.008;P = 0.047;P = 0.014;P = 0.006)中也与胰岛素抵抗风险降低相关,而rs26528等位基因仅在对照组中与胰岛素抵抗风险降低相关(P = 0.016;P = 0.021)。在450例对照和450例患者中检测了白细胞介素-27血浆水平,患者的水平显著高于对照(P = 0.004)。然而,白细胞介素-27血浆水平与基因多态性无关。荧光素酶测定表明,rs40837等位基因与miR-379-5p共转染显著降低了荧光素酶基因表达。我们的研究首次表明,IL基因多态性与早发性冠状动脉疾病及一些代谢参数相关。rs40837等位基因在miR-379-5p存在时显著降低了荧光素酶基因表达。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ad3/5610017/b2acac34ce0d/oncotarget-08-64459-g001.jpg

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