Polymorphisms of interleukin 4 receptor gene and interleukin 10 gene are not associated with Graves' disease in the UK.

Graves' disease (GD) is an autoimmune disorder of the thyroid gland and both environmental and genetic factors contribute to disease aetiology. Cytokines, such as interleukin 4 (IL-4) and interleukin 10 (IL-10), are involved in the immune response and may be implicated in the autoimmune disease process. Associations have been reported between single nucleotide polymorphisms (SNPs) of IL-10 and the Ile50Val polymorphism of the IL-4 receptor gene (IL-4R) gene and atopy and autoimmune diseases such as systemic lupus erythematosus and rheumatoid arthritis. The autoimmune diseases cluster within families and susceptibility genes may overlap between the different disorders. Therefore, we investigated 5 SNPs (-592C/A, -657G/A, - 819C/T, -1349A/G, and -2013G/A) in the promoter region of the IL-10 and the Ile50Val polymorphism (A/G) in the IL-4R in a large UK population based case-control dataset with GD. No association was found between the polymorphisms studied and GD and no significant differences were found in genotype or allele frequencies between the patients and control subjects. We conclude these polymorphisms of IL-10 and IL-4R previously associated with other immune mediated diseases, do not confer susceptibility to GD in white Caucasians in the United Kingdom.

The genetics of autoimmune endocrine disease.

The common autoimmune endocrinopathies result from an interaction between environmental factors and genetic predisposition. Several chromosomal gene regions have been shown to contribute to more than one disease, supporting the clinical observation that the autoimmune endocrine diseases cluster within individuals and families. Genetic studies have implicated the major histocompatability complex (MHC)-human leucocyte antigen (HLA) genes on chromosome 6p21, although this chromosomal region does not explain all of the genetic contribution to the various disorders. Non-MHC-HLA genes, including disease-specific loci, are beginning to be identified and the publication of the draft sequence of the human genome will undoubtedly expediate future discoveries. Combined with the establishment of large cohorts of subjects with disease and the development of technology capable of performing high-throughput genotyping, genetic studies are likely to impact on the future treatment and prevention of the common autoimmune endocrine diseases.