In:
The Journal of Clinical Endocrinology & Metabolism, The Endocrine Society, Vol. 92, No. 8 ( 2007-08-01), p. 3338-3341
Abstract:
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.
Type of Medium:
Online Resource
ISSN:
0021-972X
,
1945-7197
DOI:
10.1210/jc.2007-0173
Language:
English
Publisher:
The Endocrine Society
Publication Date:
2007
detail.hit.zdb_id:
2026217-6
