The Promoter Region of the CTLA4 Gene is Associated with Type 1 Diabetes Mellitus

The CTLA4 (cytotoxic T lymphocyte associated antigen-4) gene encodes the T cell receptor involved in the control of T cell proliferation and mediates T cell apoptosis. C-T polymorphism is present at position -318 from the ATG start codon in the promoter region of the gene. We report a study on the polymorphism in 347 unrelated children with type 1 diabetes mellitus (DM) (age at diagnosis 7.2+/-3.8 years) and their 260 healthy siblings as controls. Genotype C/C conferred a risk of type 1 DM (RR = 2.02, 95% CI 1.32-3.10, pc = 0.0033). The gene frequency of the C allele was higher in patients (RR = 1.91, 95% CI 1.28-2.84, pc = 0.0026). The gene frequency and phenotype frequency of the T allele were negatively associated with type 1 DM (RR = 0.52, 95% CI 0.35-0.78, pc = 0.0026 and RR = 0.49, 95% CI 0.32-0.76, pc = 0.0022, respectively). The frequency of genotype C/T was lower in patients (RR = 0.50, 95% CI 0.32-0.78, pc = 0.0051). This study demonstrates that nucleotide -318 C-T polymorphism of the CTLA4 gene is associated with type 1 DM. The promoter allele -318 C confers a risk of type 1 DM but allele -318 T confers protection against this disease.