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

// Rosalinda Posadas-Sánchez 1 , Nonanzit Pérez-Hernández 2 , José Manuel Rodríguez-Pérez 2 , Ramón M. Coral-Vázquez 3 , Bladimir Roque-Ramírez 4 , Luis Llorente 5 , Guadalupe Lima 5 , Carmina Flores-Dominguez 7 , Teresa Villarreal-Molina 6 , Carlos Posadas-Romero 1 and Gilberto Vargas-Alarcón 2 1 Departamento de Endocrinología, Instituto Nacional de Cardiología Ignacio Chávez, Mexico D.F., México 2 Departamento de Biología Molecular, Instituto Nacional de Cardiología Ignacio Chávez, Mexico D.F., México 3 Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Mexico D.F., México 4 Departamento de Farmacobiologia CINVESTAV-Sede Sur, Mexico D.F., México 5 Departamento de Inmunología y Reumatología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico D.F., México 6 Laboratorio de Genómica Cardiovascular, Instituto Nacional de Medicina Genómica, Mexico D.F., México 7 CICSA, Universidad Anahuac, Estado de México, México Correspondence to: Gilberto Vargas-Alarcón, email: // Keywords : association studies, coronary artery disease, inflammation, interleukin 27, polymorphism genetics Received : December 19, 2016 Accepted : March 03, 2017 Published : March 15, 2017 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 (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.