Association of CTLA4 exon-1 polymorphism with the tumor necrosis factor-α in the risk of systemic lupus erythematosus among South Indians

Cytotoxic T lymphocyte associated-antigen (CTLA4) is a potential negative regulatory molecule of T-cells and associated with several autoimmune diseases. Several reports from different ethnic groups showed that the polymorphisms of the CTLA4 gene have been associated with autoimmune diseases including SLE. Therefore, we aimed to investigate the +49 A/G polymorphism in South Indian SLE patients and its association with disease aetiology and serological markers. A total of 534 samples were genotyped for the +49 A/G polymorphism in exon 1 of the CTLA-4 gene through PCR-RFLP method. We found significant association of genotype and allele frequencies with +49 A/G polymorphism in SLE patients. The frequency of the +49 A/G polymorphism rs231775 ‘GG’ genotype was significantly higher in patients with SLE (12.32%) than those in healthy control subjects (4.6%) (OR: 1.797; 95% CI 1.264–2.554; p = 0.001). The frequency of mutant allele ‘G’ also found to be significantly higher in cases (36.01%) than controls (24.92%) (OR: 1.695, 95% CI: 1.298–2.214, p < 0.001). We observed significant increase in serum TNF-α, interferon-α, IL-10 and IL-12 in SLE cases compared to controls. We also found a significant association of serum TNF-α, interferon-α, IL-10 and IL-12 with SLE phenotypes. In addition there was a significant increase in serum TNF-α level in “GG” genotype SLE subjects suggesting that it might play a major role in the advancement of SLE disease.