Interleukin 1 receptor antagonist polymorphisms are associated with the risk of developing acute coronary syndrome in Mexicans

Abstract

Inflammation plays an essential role in the development and progression of atherosclerotic lesions. Cytokines of the interleukin-1 family are central regulators in immunoinflammatory mechanisms. In the present work, the role of interleukin 1 (IL-1) and IL-1 receptor antagonist (IL-1RN) gene polymorphisms as susceptibility markers for acute coronary syndrome (ACS) was evaluated. Six polymorphisms in the IL-1 gene cluster members were genotyped by 5' exonuclease TaqMan genotyping assays in 289 ACS patients and 248 healthy controls. Haplotypes were constructed after linkage disequilibrium analysis. Statistically significant associations were found between three polymorphisms of the IL-1RA gene (rs419598, rs315951, and rs2234663) and the development ACS. The polymorphism RN.4T>C (rs419598) was associated with hypertension, previous myocardial infarction, and major adverse cardiac events. To establish the functional effect of the IL-1RN6/2 (rs315951) polymorphism (principal IL-1RN polymorphism associated with ACS in our study), monocytes were obtained from a group of 27 healthy individuals and the production of IL-1 receptor antagonist (IL-1Ra) was determined. Monocytes from individuals with rs315951 CC genotype showed similar production of IL-1Ra as individuals with GG and CG genotypes. The analysis of linkage disequilibrium of the IL-1RA polymorphisms showed four out of eight different possible allele combinations with differences between the studied groups. Patients with ACS showed increased frequency of "T1C" haplotype when compared to healthy controls. The results suggest that IL-1RN gene polymorphisms could be involved in the risk of developing ACS in Mexican individuals.