A cytotoxic T lymphocyte antigen-4 (CTLA-4) gene polymorphism is associated with autoimmune Addison's disease in English patients

OBJECTIVE Recent studies have demonstrated an association between a microsa tellite polymorphism of the CTLA-4 gene, specifically a 106 base pair allel e, and both Graves' disease and autoimmune hypothyroidism, The aim of the p resent study was to determine whether the same polymorphism of the CTLA-4 g ene was associated with autoimmune Addison's disease. DESIGN AND PATIENTS We analysed a microsatellite polymorphism (variant leng ths of a dinucleotide (AT), repeat) within exon 3 of the CTLA-4 gene in the following groups: 21 English patients with non-associated Addison's diseas e, 18 with autoimmune polyglandular syndrome type 2 (APS2) and 173 healthy control subjects; 26 Norwegian patients with nonassociated Addison's diseas e, 9 with autoimmune polyglandular syndrome type 1 (APS1), 17 with APS2 and 100 controls; 3 Finnish patients with non-associated Addison's disease, 5 with APS2 and 71 controls; 10 Estonian patients with non-associated Addison 's disease, 2 with APS2 and 45 controls. MEASUREMENTS The CTLA-4 microsatellite gene polymorphisms were determined b y polymerase chain reaction amplification of genomic DNA and resolution of the products on sequencing gels. RESULTS The frequency of the 106 base pair allele was significantly increas ed in the groups of English patients with either non-associated Addison's d isease or APS2 (P = 0.02 and 0.04, respectively), when compared to healthy controls with no clinical evidence or family history of either Addison's di sease or any other autoimmune disorder. For Norwegian patients with either non-associated Addison's disease, APS1 or APS2, there was no association (P = 0.69, 0.62 and 0.97, respectively). This was also the case for Finnish p atients with either non-associated Addison's disease or APS2 (P = 0.23 and 0.28, respectively) and for Estonian patients with either non-associated Ad dison's disease or APS2 (P = 0.34 and 0.29, respectively). CONCLUSIONS These results indicate that differences exist in the frequency of the 106 base pair allele in different population groups and in only the English population was the 106 base pair allele associated with Addison's d isease.