Role of <i>CTLA4</i> A49G polymorphism in systemic lupus erythematosus and its geographical distribution

CTLA-4 (cytotoxic T-lymphocyte-associated protein-4) or CD152 is an inhibitory receptor expressed constitutively on CD4+ CD25+ T regulatory lymphocytes and transiently on activated CD4+ and CD8+ T lymphocytes. Its inhibitory function promotes long-lived anergy in immune cells and prevents autoimmunity. Therefore, it plays a crucial role in T cell-mediated autoimmunity, and thus in susceptibility to autoimmune diseases, including systemic lupus erythematosus (SLE). It is encoded by CTLA4 gene in humans. AtoG polymorphism at position +49 of CTLA4 gene is the only polymorphism which changes amino acid sequence from alanine to threonine in the leader sequence, which may affect the function of CTLA-4. Association of CTLA4 polymorphisms with SLE has been investigated in several reports in different ethnic populations from different countries, which have shown highly inconsistent findings. In this review, we have compiled previous studies which have reported the association of CTLA4 A49G polymorphism in SLE and its geographical distribution.