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 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 (Pdominant = 0.046; Pover-dominant = 0.002; Pco-dominant1 = 0.007 for rs26528T; Pover-dominant = 0.008 and Pco-dominant1 = 0.031 for rs40837). The rs40837 A allele was also associated with a lower risk of insulin resistance, in cases (Pover-dominant = 0.037) and controls (Padditive = 0.008; Pdominant = 0.047; Precessive = 0.014; Pco-dominant2 = 0.006), while the rs26528 T allele was associated with a lower risk of insulin resistance only in the control group (Precessive = 0.016; Pco-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.
Highlights
Cardiovascular disease (CVD) is the main cause of morbidity in developed and emerging countries
As far as we know, this is the first study reporting the association of IL-27p28 gene polymorphisms with premature Coronary arterial disease (CAD) (pCAD)
We analyzed the distribution of rs26528, rs17855750, rs181206 and rs40837 in pCAD cases and controls in order to determine whether they confer susceptibility to pCAD
Summary
Cardiovascular disease (CVD) is the main cause of morbidity in developed and emerging countries. Macrophage and T cell infiltrates are known to play an important role in atherosclerotic lesions in humans and in animal models [5,6]. Macrophages [7,8] and Th1 cells [9,10,11] secreted cytokines and chemokines that amplify local immune responses, while Th2 cells are known to have a protective effect on the development of atherosclerosis [12,13]. IL-27 is expressed in atherosclerotic plaques [22], and its role in atherosclerosis has been studied in cultured cells, animal models and coronary patients, with inconsistent findings. Coronary patients showed higher IL-27 levels as compared to controls, and IL-27 levels showed a significant correlation with stenosis severity [24]
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