Common Variants in IL-20 Gene are Associated with Subclinical Atherosclerosis, Cardiovascular Risk Factors and IL-20 Levels in the Cohort of the Genetics of Atherosclerotic Disease (GEA) Mexican Study.

Javier Angeles-Martínez,Gilberto Vargas-Alarcón,Rosalinda Posadas-Sánchez,Eyerahi Bravo-Flores,María Del Carmen González-Salazar

doi:10.3390/biom10010075

Abstract

Inflammation has been involved in the development of atherosclerosis, type 2 diabetes mellitus, insulin resistance, and obesity. Interleukin 20 is a pro-inflammatory cytokine encoded by a polymorphic gene located in chromosome 1. The aim of the study was to evaluate the association of two IL-20 polymorphisms (rs1400986 and rs1518108) with subclinical atherosclerosis (SA), cardiovascular risk factors and IL-20 levels in a cohort of Mexican individuals. The polymorphisms were determined in 274 individuals with SA and 672 controls. Under different models, rs1400986 (OR = 0.51, Pcodominant1 = 0.0001; OR = 0.36, Pcodominant2 = 0.014; OR = 0.49, Pdominant = 0.0001 and OR = 0.55, Padditive = 0.0001) and rs1518108 (OR = 0.62, Pcodominant2 = 0.048 and OR = 0.79, Padditive = 0.048) were associated with a lower risk of SA. These polymorphisms were associated with cardiovascular risk factors in individuals with SA and controls. Controls with the rs1400986 TT genotype presented high levels of IL-20 (p = 0.031). In individuals with the rs1400986 CC genotype, we observed a negative correlation between IL-20 levels and total abdominal tissue (TAT), visceral abdominal tissue (VAT) and subcutaneous abdominal tissue (SAT). Our results indicate that the IL-20 rs1400986 and rs1518108 polymorphisms were associated with decreased risk of developing SA and with some cardiovascular risk factors in individuals with SA and healthy controls. Negative correlation between BMI and VAT/SAT ratio in individuals with rs1400986 CC genotype and among IL-20 levels and TAT, VAT and SAT was observed.

Highlights

Cardiovascular disease, principally coronary artery disease (CAD) is the leading cause of preventable death worldwide [1]
Our study presents some strengths: The group of individuals that we analyzed belong to the Genetics of Atherosclerotic Disease (GEA) project that was designed to examine the genetic bases of premature CAD and subclinical atherosclerosis (SA) and its association with emerging and traditional cardiovascular risk factors in the Mexican population
Our results indicate that the rs1400986 and rs1518108 polymorphisms in the IL-20 gene were associated with decreased risk of developing SA

Summary

Introduction

Cardiovascular disease, principally coronary artery disease (CAD) is the leading cause of preventable death worldwide [1]. IR and T2DM are thought to be mechanistically linked to CAD via subclinical. SA develops over several decades and often remains asymptomatic until the occurrence of an acute, life-threatening event. Two subclinical measures of atherosclerosis have been used to predict CAD. One is carotid intima-media thickness (cIMT), a measure of the intimal and medial layers of the carotid artery walls and the other is coronary artery calcification (CAC), a marker of subclinical coronary atherosclerosis [5,6]. Visceral adipose tissue (VAT) accumulation is clearly associated with a higher risk of T2DM and CAD and is positively associated with cardiovascular risk factors [7,8,9]. It is well known that inflammation plays an important role in the development of

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