Background: Addison's disease (AD) is an autoimmune disorder caused by the destruction of the adrenal gland by the lymphocytes in genetically susceptible individuals. The contribution of HLA genes to the genetic risk to AD has been known for a long time; however, non-HLA genetic factors are likely to be required for the development of the disease. Several studies have associated the CD28/CTLA4 region on chromosome 2q33 with the disease in different populations. The cytotoxic T lymphocyte-associated antigen 4 (CTLA4) gene encodes a receptor involved in the control of T cell proliferation and mediates T cell apoptosis.
Aim: To determine the contribution of two polymorphisms of the CTLA4 to the disease; the A/G dimorphism at position +49 in exon 1 and the (AT)n microsatellite in the 3' untranslated region of exon 3.
Patients: Fifty seven patients with autoimmune AD (autoimmunity for anti 21-hydroxylase was confirmed) and 111 unrelated healthy subjects from the general populations were analyzed as controls.
Methods: Restriction enzyme digestion of polymerase chain reaction (PCR) amplified genomic DNA for the A/G dimorphism and PCR followed by high-resolution electrophoresis for the (AT)n microsatellite. For disease association studies, the case-control approach was used.
Results: The frequency of the A allele of 49 A/G polymorphism was 65.79% in the patients compared with 72.07% in the control group. These differences were not significant. Analysis of the (AT)n polymorphism identified 19 different alleles, ranging from 262 to 308 bp in length, but no allele was significantly associated with the disease.
Conclusions: Our results did not show any evidence of association of any of the CTLA4 gene polymorphisms with the disease. This might result from population-specific differences in genetic and environmental susceptibility to AD.