Context: A recent large-scale analysis of non-synonymous coding polymorphisms showed strong evidence that an alanine to threonine amino acid change at codon 946 of the interferon-induced helicase (IFIH1) gene (SNP ID rs1990760) was associated with type 1 diabetes. Previous investigations have also demonstrated that an intronic polymorphism (termed PD1.3; SNP ID rs11568821) in the programmed cell death (PDCD1) gene was associated with systemic lupus erythematosus and rheumatoid arthritis.

Objective: We sought to replicate these genetic associations in Graves' disease and autoimmune Addison's disease patient cohorts.

Patients and Methods: Six hundred and two Graves' disease subjects, 214 Addison's disease subjects and 446 healthy controls were genotyped for the IFIH1 and PDCD1 single nucleotide polymorphisms using mass spectrometer analysis of primer extension products (Sequenom).

Results: The alanine carrying allele at the IFIH1 codon 946 polymorphism was present in 796 of 1204 (66%) GD patient alleles compared to 508 of 892 (57%) control subject alleles; odds ratio 1.47 (5-95% CI 1.23 to 1.76), p=1.9x10^-5. In contrast, there was no association of alleles at this marker in autoimmune Addison's disease. Neither was there evidence for association in either patient cohort at the PD1.3 polymorphism.

Conclusions: We confirm a significant contribution of the Ala946Thr IFIH1 polymorphism to organ-specific autoimmune diseases, extending the range of conditions associated with this variant to include Graves' disease. This polymorphism may also contribute to several other autoimmune disorders.