Because the functional single-nucleotide polymorphism (SNP) rs231775 of the CTLA-4 gene is associated with autoimmune diseases and because of the critical role of the immune reaction in sepsis, we intended to examine the effect of this polymorphism on survival in patients with sepsis.
It has been found that CTLA4 +49A>G (rs231775), +6230G>A (rs3087243), and 11430G>A (rs11571319) polymorphisms are associated with susceptibility to many autoimmune diseases, and can down-regulate the inhibition of cellular immune response of CTLA4.
Its nonsynonymous polymorphism +49G > A (dbSNP: rs231775) has been linked to an elevated risk of T-cell-mediated autoimmune diseases, infectious diseases, and even carcinomas.
Interestingly, we have recently shown that an SNP in the CTLA-4 coding region (49A > G) is also associated with susceptibility to human cancer, but the risk allele for susceptibility to cancer (allele A) is the opposite of that found for susceptibility to autoimmune disease (allele G), which has been confirmed by a meta-analysis of reported studies.
While there was no association with vitiligo overall, the meta-analysis showed significant association of SNP rs231775 in that subgroup of vitiligo patients who also had other concomitant autoimmune diseases.
The cytotoxic T lymphocyte-associated antigen (CTLA)-4 molecule plays an important role in immune regulation by downregulating T-cell activation, and the CTLA-4 49A/G polymorphism in the exon 1 has been shown to be associated with a number of autoimmune diseases.
Gene polymorphisms involving CTLA-4 promoter (-318 C/T), exon 1 (49 A/G), and exon 4 (microsatellite (AT)n) have been linked to Hashimoto's thyroiditis (HT) and other autoimmune diseases.