The CTLA4 +49 A/G (rs231775) polymorphism influences susceptibility to SLE in South Indian Tamils.

Systemic lupus erythematosus (SLE) is a prototype autoimmune disease with complex etiology. Loss of immune tolerance and synthesis of autoantibodies against nuclear antigens contributes to the disease. Genetic aberrations disrupting the functions of immune regulatory receptors may facilitate the development of autoimmune diseases. Cytotoxic T-lymphocyte antigen 4 (CTLA4) is an inhibitory receptor for T cells and this study was carried out to analyze the influence of CTLA4 +49A/G (rs231775) polymorphism on susceptibility to SLE in ethnic Tamils. Three hundred SLE patients and 460 age and sex similar, ethnicity-matched controls were screened for the +49 A/G polymorphism by real time polymerase chain reaction (PCR). The wild allele (A) frequency in controls and cases was 63% and 47%, respectively. The presence of heterozygous (AG) and homozygous mutant (GG) genotype was associated with a significant risk to develop SLE (P = 0.0001, OR-2.29, 95% confidence interval (CI), 1.6-3.3) and (P = 0.0001, OR-4.3, 95% CI, 2.8-6.99). The frequency of mutant allele (G) in patients was also significantly associated with SLE (P = 0.0001, OR-1.9, 95% CI, 1.5-2.4). However, this polymorphism did not influence the clinical or serological phenotypes in our study. Therefore the CTLA4 +49 A/G polymorphism is a potential genetic risk factor for lupus susceptibility in South Indian Tamils, but does not appear to influence either the clinical or serological phenotype.