Oncotarget

Clinical Research Papers:

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

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

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Oncotarget. 2017; 8:64459-64470. https://doi.org/10.18632/oncotarget.16223

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Abstract

Rosalinda Posadas-Sánchez1, Nonanzit Pérez-Hernández2, José Manuel Rodríguez-Pérez2, Ramón M. Coral-Vázquez3, Bladimir Roque-Ramírez4, Luis Llorente5, Guadalupe Lima5, Carmina Flores-Dominguez7, Teresa Villarreal-Molina6, Carlos Posadas-Romero1 and Gilberto Vargas-Alarcón2

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 (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.


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