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

Several studies suggest an important role of Interleukin-27 in the development of atherosclerosis. The aim of this study was to establish whether the IL-27p28 gene polymorphisms are associated with premature coronary artery disease and/or other cardiovascular risk factors. Four IL-27p28 gene polymorphisms were selected and genotyped in 1162 premature coronary artery disease cases and 1107 controls. rs26528 T and rs40837 A 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 A 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 T 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 IL-27p28 polymorphisms. Luciferase assays showed that co-transfection of the rs40837 A allele and miR-379-5p significantly decreased luciferase gene expression. Our study shows for the first time, that IL-27p28 gene polymorphisms are associated with premature coronary artery disease and with some metabolic parameters. The rs40837 A allele in presence of miR-379-5p significantly decreased luciferase gene expression.