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Genomic polymorphism at the interferon-induced helicase (IFIH1) locus contributes to Graves' disease susceptibility

Lookup NU author(s): Dr Alison Sutherland, Jocelyn Davies, Dr Kate Owen, Professor Timothy Cheetham, Dr Robert James, Dr Petros Perros, Dr Peter Donaldson, Professor Heather Cordell, Dr Richard Quinton, Professor Simon PearceORCiD



Context: A recent large-scale analysis of nonsynonymous 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: A total of 602 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%) Graves' disease patient alleles compared with 508 of 892 (57%) control subject alleles [odds ratio 1.47 (5-95% confidence interval, 1.23-1.76); P = 1.9 × 10-5]. 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. Copyright © 2007 by The Endocrine Society.

Publication metadata

Author(s): Sutherland A, Davies JM, Owen CJ, Vaikkakara S, Walker C, Cheetham TD, James RA, Perros P, Donaldson PT, Cordell HJ, Quinton R, Pearce SHS

Publication type: Article

Publication status: Published

Journal: Journal of Clinical Endocrinology & Metabolism

Year: 2007

Volume: 92

Issue: 8

Pages: 3338-3341

ISSN (print): 0021-972X

ISSN (electronic): 1945-7197

Publisher: The Endocrine Society


DOI: 10.1210/jc.2007-0173

PubMed id: 17535987


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Funder referenceFunder name
Wellcome Trust
G84/5959Medical Research Council