Systemic lupus erythematosus and genetic variation in the interleukin 1 gene cluster: a population based study in the southeastern United States

Background: Interleukin (IL)1α and IL1β, and their endogenous receptor antagonist (IL1Ra), have been related to the pathology of systemic lupus erythematosus (SLE), but the role of IL1 polymorphisms in the aetiology of SLE is unknown. Objective: To examine polymorphisms at IL1α −889(C→T), IL1α +4845(C→T), IL1β −511(C→T), IL1β +3953(G→T), and IL1Ra (86 bp VNTR) in a population based study of SLE in North Carolina and South Carolina. Methods: Genotypes from 230 cases who met ACR classification criteria, and from 275 controls matched for age, sex, and state, were analysed separately for African Americans and whites. Odds ratios (ORs) were estimated by logistic regression models for each locus alone and also after adjusting for polymorphisms at adjacent loci. Results: An increased risk of SLE for the IL1α −889C/C genotype compared with carriage of the −889T allele was found in both African Americans (OR = 3.1, p = 0.001) and whites (OR = 2.9, p = 0.005). In African Americans, carriage of the IL1β −511T allele was associated with a higher risk of SLE than carriage of the −511C/C genotype (OR = 2.4, p = 0.017), independent of variation at IL1α −889. Conclusions: The observed associations support the hypothesis that genetic variation in IL1 is involved in the aetiology of SLE and merit further investigation.