IL-37 Gene and Cholesterol Metabolism: Association of Polymorphisms with the Presence of Hypercholesterolemia and Cardiovascular Risk Factors. The GEA Mexican Study.

Fabiola López-Bautista,José Manuel Fragoso,Gilberto Vargas-Alarcón,Christian Vázquez-Vázquez,Rosalinda Posadas-Sánchez,José Manuel Rodríguez-Pérez

doi:10.3390/biom10101409

Fabiola López-Bautista, José Manuel Fragoso + Show 4 more

Open Access

https://doi.org/10.3390/biom10101409

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Journal: Biomolecules	Publication Date: Oct 5, 2020
Citations: 13	License type: CC BY 4.0

Affiliation: Instituto Nacional de Cardiología

Abstract

Interleukin 37 (IL-37) is an anti-inflammatory cytokine involved in the regulation of cholesterol homeostasis, reducing the levels of plasma cholesterol, fatty acids, and triglycerides. The aim of the present study was to evaluate the association of the IL-37 polymorphisms with the presence of hypercholesterolemia (HC), and with cardiovascular risk factors. Nine IL-37 polymorphisms (rs2708965, rs2708962, rs6717710, rs2708961, rs2708960, rs2708958, rs2723187, rs2708947, and rs2723192) were determined by TaqMan assays in a group of 1292 individuals (514 with and 778 without hypercholesterolemia) belonging to the cohort of the GEA Mexican Study. The associations were evaluated by logistic regression, using inheritance models adjusted by confounding variables. Under codominant 1 model, the rs2708961 (OR = 0.51, p = 0.02), rs2723187 (OR = 0.35, p = 0.005), and rs2708947 (OR = 0.49, p = 0.02) polymorphisms were associated with low risk of HC. The association of the polymorphisms with cardiovascular risk factors was evaluated independently in HC and non-HC individuals. In non-HC individuals, some polymorphisms were associated with the risk of having high levels of LDL-C, glucose, and high risk of T2DM, and low risk of having high visceral abdominal fat. On the other hand, in individuals with HC five, polymorphisms were associated with high levels of C-reactive protein. The IL-37 rs2708961, rs2723187, rs2708947 polymorphisms were associated with low risk of HC, and some IL-37 polymorphisms were associated with cardiometabolic factors in both individuals with and without HC.

Highlights

Coronary artery disease (CAD) is a chronic, progressive, and multifactorial disease modulated by genetic and environmental factors [1]
The increased uptake of oxidized low-density lipoprotein and/ or reduced cholesterol efflux leads to the deposition of esterified cholesterol in the cytoplasm of macrophages and the generation of foam cells [4]
Our data suggest an association of the rs2708961, rs2723187, and rs2708947 polymorphisms in the Interleukin 37 (IL-37) gene with a low risk of HC

Summary

Introduction

Coronary artery disease (CAD) is a chronic, progressive, and multifactorial disease modulated by genetic and environmental factors [1]. The role of IL-37 in the regulation of cholesterol homeostasis was demonstrated in a transgenic mouse model for IL-37 These mice were fed a high-fat diet for 16 weeks, showing reduced levels of plasma cholesterol, fatty acids, and triglycerides when compared to wild mice [11]. These researchers showed that the mechanism by which IL-37 could be participating in in the macrophage lipid-handling involves AMP-activated kinase (AMPK), an important signaling protein downstream of IL-37. Based on a bioinformatic analysis, we selected the rs2708965, rs2708962, rs6717710, rs2708961, rs2708960, rs2708958, rs2723187, rs2708947, and rs2723192 polymorphisms for the present study

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