Interleukin 1 receptor antagonist (IL1Ra) VNTR polymorphism influences circulatory IL1Ra levels and development of SLE in South Indian Tamils

Background Systemic lupus erythematosus (SLE) is a systemic autoimmune disease with complex aetiology. Genetic polymorphisms disrupting the functions of genes encoding anti-inflammatory cytokines such as IL1Ra may influence the disease activity and outcome in SLE. In this study, the IL1Ra VNTR polymorphism was tested for its influence on disease susceptibility, clinical and serological phenotypes of SLE in South Indian Tamils. Materials and methods Three hundred SLE patients and 460 age, sex and ethnicity matched controls were genotyped for IL1Ra VNTR polymorphism by PCR. Serum IL1Ra was quantified by ELISA. Results Genotyping revealed that the four and two repeats were the most frequent polymorphic alleles in our subjects. The two repeat allele (A2) was more frequent in SLE (18%) than in controls (9%) and it conferred a significant risk to develop SLE [p=0.0001, OR 2.36, 95% CI, 1.7–3.2]. However, incidence of heterozygous genotype (A1A2) was high among SLE patients (25%) and presence of which was observed to influence the development of SLE [p=0.0001, OR 5.8, 95% CI, 3.2–9.5]. Quantification of serum IL1Ra revealed that the four repeat allele was associated with the normal production of the cytokine, whereas the other variants were associated with the reduced expression of the IL1Ra. Conclusion IL1Ra VNTR polymorphism analysis in South Indian Tamil SLE patients revealed that the genotype A1A2 was associated with lupus susceptibility. The VNTR polymorphism encoding the allele with two repeats was associated with reduced circulatory concentration of IL1Ra in SLE patients, likely predisposing them to develop clinically severe form of the disease.