Polymorphisms of IL-1β, IL-1Ra, and TNF-α genes: A nested case-control study of their association with risk for stroke

Abstract

Certain alleles of cytokine genes interleukin-1 beta (IL-1beta), interleukin-1 receptor antagonist (IL-1Ra), and tumor necrosis factor alpha (TNF-alpha) are correlated with increased production of the proteins. The aim of this study was to investigate polymorphisms of these genes and their possible correlation with the development of stroke. This matched case-control study was nested within the population-based Västerbotten Intervention Program (VIP) cohort and the Northern Sweden World Health Organization MONICA (Multinational Monitoring of Trends and Determinants in Cardiovascular Diseases) cohort, based on individuals who were free from cardiovascular events when the cohorts were established. After an average period of 34.1 months, 113 individuals developed stroke and to each case 2 individuals not suffering from cardiovascular events were matched to serve as controls. Polymerase chain reaction amplification was used to analyze genetic polymorphisms. There was no association between polymorphic sites of the IL-1beta and IL-1Ra genes and stroke. Carriage of haplotype A2+IL-1beta/A2+IL-1Ra was significantly increased in normotensive cases (23.1%) compared with normotensive controls (8.9%) (odds ratio [OR] = 3.07; P = .045). In hypertensive male cases, there was an association between the A1A1 genotype of TNF-alpha and risk of stroke (OR = 2.46; P = .034). Our findings indicate an association between allele A1 of the TNF-alpha NcoI polymorphism and stroke in hypertensive male cases, as well as an association between haplotype A2+IL-1beta/A2+IL-1Ra and stroke in normotensive cases.