Cytotoxic T-lymphocyte associated protein 4 (CTLA4) polymorphisms are linked to systemic lupus erythematosus: an updated meta-analysis.

Cytotoxic T-lymphocyte associated protein 4 (CTLA-4) molecule controls T cell immune response. Functional single nucleotide polymorphisms (SNPs) in the CTLA-4 gene have been associated with several autoimmune diseases, including systemic lupus erythematosus (SLE).  However, the genetic association of the CTLA-4 variants with vulnerability to SLE remained contradictory. We have conducted a current meta-analysis by combining the findings of prior published articles in order to make a conclusive statement. Various literature databases were screened with appropriate keywords to obtain relevant articles, and eligible reports were obtained using well-defined inclusion and exclusion criteria. Meta-analysis was performed by Comprehensive Meta-analysis V 3.3, and various statistical parameters such as odds ratio, 95% confidence interval, and probability values were computed. A total of 3847 SLE patients and 5278 healthy controls were considered in the present meta-analysis from 26 individual reports. A significant association of CTLA-4 +49 A/G (G vs. A: p=0.03, OR=1.47) and -1722 T/C (p=0.02, OR=0.87) polymorphisms were observed with susceptibility and resistance against the development of SLE, respectively. However, the other two SNPs in the CTLA-4 gene (-318 C/T and -1661 A/G) failed to establish a connection. Interestingly, subgroup analysis revealed an association of CTLA-4 +49 A/G with a predisposition to SLE only in the Asian population (G vs. A: p=0.04, OR=1.26, GG vs. AA: p=0.02, OR=1.84, AG vs AA: p=0.01, OR=1.44, GG+AG vs AA: p=0.01, OR=1.52) and not in Caucasians. The current meta-analysis suggests a significant CTLA-4 +49 A/G variant association with susceptibility to SLE development in overall and Asian populations. In contrast, the other variant, -1722 T/C, is linked with protection against SLE. However, further case-control studies in diverse ethnic populations are requisite.