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

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 <i>IL-27p28</i> gene polymorphisms are associated with premature coronary artery disease and/or other cardiovascular risk factors. Four <i>IL-27p28</i> gene polymorphisms were selected and genotyped in 1162 premature coronary artery disease cases and 1107 controls. rs26528 <i>T</i> and rs40837 <i>A</i> alleles were significantly associated with a lower risk of premature coronary artery disease under different inheritance models (P_dominant = 0.046; P_{over-dominant} = 0.002; P_co-dominant1 = 0.007 for rs26528T; P_{over-dominant} = 0.008 and P_co-dominant1 = 0.031 for rs40837). The rs40837 <i>A</i> allele was also associated with a lower risk of insulin resistance, in cases (P_{over-dominant} = 0.037) and controls (P_additive = 0.008; P_dominant = 0.047; P_recessive = 0.014; P_co-dominant2 = 0.006), while the rs26528 <i>T</i> allele was associated with a lower risk of insulin resistance only in the control group (P_recessive = 0.016; P_co-dominant2 = 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 <i>IL-27p28</i> polymorphisms. Luciferase assays showed that co-transfection of the rs40837 <i>A</i> allele and miR-379-5p significantly decreased luciferase gene expression. Our study shows for the first time, that IL<i>-27p28</i> gene polymorphisms are associated with premature coronary artery disease and with some metabolic parameters. The rs40837 <i>A</i> allele in presence of miR-379-5p significantly decreased luciferase gene expression.