title: Association of Graves' disease with an allele of the interleukin-1 receptor antagonist gene.
abstract: The proinflammatory cytokine, interleukin-1 (IL-1), has been implicated in the pathogenesis of several autoimmune and inflammatory diseases. One of its natural inhibitors, IL-1 receptor antagonist, is a potent antiinflammatory agent. We have previously described genetic associations between an allele of the IL-1 receptor antagonist gene (IL1RN*2) and several autoimmune and inflammatory diseases. In the present study, we tested the association of this polymorphism with thyroid diseases. We genotyped 2 separate cohorts (total of 100 patients) with Graves' disease and 58 patients with Hashimoto's thyroiditis and compared IL1RN*2 frequencies with those in 261 ethnically matched controls. There was a significant increase in IL1RN*2 frequency and carriage rate in Graves' disease, but this was not associated with thyroid antibody levels, T4 levels, thyroid-associated ophthalmopathy, or outcome after antithyroid drug treatment. In contrast, there was no difference in the frequency of IL1RN*2 between patients with Hashimoto's thyroiditis and the control group. Whether the IL1RN polymorphism makes a direct functional contribution to the pathogenesis of Graves' disease or is acting as a marker for a linked gene is being investigated.
authors.affiliation: Department of Medicine and Pharmacology, University of Sheffield, Royal Hallamshire Hospital, United Kingdom.
authors.forename: A I
authors.initials: AI
authors.lastname: Blakemore
authors.forename: P F
authors.initials: PF
authors.lastname: Watson
authors.forename: A P
authors.initials: AP
authors.lastname: Weetman
authors.forename: G W
authors.initials: GW
authors.lastname: Duff
mesh_terms: D000483:Alleles; D013956:Antithyroid Agents / Q000627:therapeutic use; D015331:Cohort Studies; D005128:Eye Diseases / Q000209:etiology; D005260:Female; D005796:Genes; D005838:Genotype; D006111:Graves Disease / Q000150:complications / Q000235:genetics* / Q000503:physiopathology; D006801:Humans; D008297:Male; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors*; D013967:Thyroiditis, Autoimmune / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology
chemical_list: D013956:Antithyroid Agents; D017472:Receptors, Interleukin-1