Interferon Regulatory Factor 5 (IRF5) Gene Haplotypes Are Associated with Premature Coronary Artery Disease. Association of the IRF5 Polymorphisms with Cardiometabolic Parameters. The Genetics of Atherosclerotic Disease (GEA) Mexican Study.

Rosalinda Posadas-Sánchez,José Manuel Fragoso,Gilberto Vargas-Alarcón,Guillermo Cardoso-Saldaña

doi:10.3390/biom11030443

Interferon Regulatory Factor 5 (IRF5) Gene Haplotypes Are Associated with Premature Coronary Artery Disease. Association of the IRF5 Polymorphisms with Cardiometabolic Parameters. The Genetics of Atherosclerotic Disease (GEA) Mexican Study.

Rosalinda Posadas-Sánchez, José Manuel Fragoso + Show 2 more

Open Access

https://doi.org/10.3390/biom11030443

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Journal: Biomolecules	Publication Date: Mar 17, 2021
Citations: 3	License type: CC BY 4.0

Affiliation: Instituto Nacional de Cardiología

Abstract

Interferon regulatory factor 5 (IRF5) has an important role in the inflammatory process, a fundamental component of coronary artery disease (CAD). Thus, the objective of this study was to evaluate the association of IRF5 polymorphisms with the development of premature CAD (pCAD) and cardiometabolic parameters. IRF5 polymorphisms (rs1874330, rs3778754, rs3757386, rs3757385, rs3807134, rs3807135, and rs6968563) were determined in 1116 pCAD patients and 1003 controls. Polymorphism distribution was similar in patients and controls; however, the haplotype analysis showed five haplotypes with a different distribution. TGCGTCT (OR (odds ratio) = 1.248, p = 0005) and TCTGCCT (OR = 10.73, p < 0.0001) were associated with a high risk, whereas TCCGTCT (OR = 0.155, p < 0.0001), CGCTTTT (OR = 0.108, p < 0.0001), and TCCGCCT (OR = 0.014, p < 0.0001) were associated with a low risk of pCAD. Associations with aspartate aminotransferase, hypertriglyceridemia, magnesium deficiency, triglycerides/HDL-C index, LDL-C, and adiponectin levels were observed in pCAD patients. In controls, associations with hypoalphalipoproteinemia, non-HDL-C, apolipoprotein B, hyperuricemia, TNF-α, IL-6, IL-15, valvular calcification, and subclinical hypothyroidism were observed. In summary, five haplotypes were associated with pCAD, two with high risk and three with low risk. Some IRF5 polymorphisms were associated with cardiometabolic parameters in pCAD patients and control.

Highlights

Coronary artery disease (CAD), a clinical manifestation of atherosclerosis, is one of the leading causes of death and morbidity worldwide [1]
Interferon regulatory factor 5 (IRF5) is expressed in monocytes and macrophages and has an important role in defining the inflammatory macrophage phenotype [5]
It has been reported that IRF5 participates in the Akt2 activation, producing an increase of glycolysis and M1 macrophage polarization [6]

Summary

Introduction

Coronary artery disease (CAD), a clinical manifestation of atherosclerosis, is one of the leading causes of death and morbidity worldwide [1]. The role of inflammation is well known in the progression of atherosclerosis. The infiltration of several types of cells, including T cells and macrophages, in the atherosclerotic plaque has been reported [2]. The production of cytokines, chemokines, and growth factors by these cells perpetuates the damage in the atherosclerotic lesion [3]. Interferon regulatory factor 5 (IRF5) plays a central role in inflammation, mediating the production of proinflammatory cytokines, such as IL-6, IL-12, IL-23, and TNF-α [4,5]. It has been reported that IRF5 participates in the Akt activation, producing an increase of glycolysis and M1 macrophage polarization [6]. M1 macrophages can produce proinflammatory cytokines and are suggested to be involved in the development of atherosclerosis and affect the stabilization and impact of atherosclerotic plaques [7,8]. Seneviratne et al, using an animal model, established that IRF5 promotes the presence of proinflammatory CD11c+

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