Graves' disease (GD) is an autoimmune disorder of the thyroid gland, of which the aetiology is unknown, but susceptibility to disease is thought to result from both genetic and environmental factors. Familial clustering data suggests that GD is a polygenic disorder, with laboratory studies identifying the HLA gene region and the CTLA-4 gene region as susceptibility loci. However, together the HLA region and the CTLA-4 gene regions only contribute about 50% towards the genetic susceptibility to GD, therefore, suggesting that other genes must also be playing a role. The interleukin-12 p40 (IL12B) gene on chromosome 5q33-34 is involved in the differentiation of T lymphocytes into the Th1 pathway. The latter is characterized by the production of cytokines that promote cell-mediated immunity making IL12B an ideal candidate gene for involvement in autoimmune diseases such as GD. A recent study reported genetic linkage and linkage disequilibrium of a 3' UTR polymorphism of the IL12B gene with type 1 diabetes, indicating that this gene may play a role in genetic susceptibility to the development of autoimmune disease. We typed 665 patients with GD, 862 control subjects and 212 families for the 3' UTR polymorphism by PCR-RFLP. All subjects taking part in the study gave informed, written consent and the study was approved by the local ethics committee. Results revealed no significant difference in allele or genotype frequency of this polymorphism between subjects with GD and controls (Allele: chi = 0.309;p = 0.578, Genotype chi = 1.839;p = 0.399). Similarly no significant transmission disequilibrium of either allele was seen in the families (chi = 0; p = 0.99). These data suggest that this polymorphism in the 3'UTR of the IL12B gene is not contributing to the genetic susceptibility to the development of Graves' disease in the UK.
08 - 11 Apr 2002
British Endocrine Societies