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1: J Clin Endocrinol Metab. 2008 Mar;93(3):1077-81. Epub 2007 Dec 11.
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Interleukin (IL)-23 receptor is a major susceptibility gene for Graves' ophthalmopathy: the IL-23/T-helper 17 axis extends to thyroid autoimmunity.

Huber AK, Jacobson EM, Jazdzewski K, Concepcion ES, Tomer Y.

Division of Endocrinology, The Vontz Center, ML 0547, University of Cincinnati College of Medicine, 3125 Eden Avenue, Cincinnati, Ohio 45267, USA. huberak@uc.edu

CONTEXT: IL-23 and its receptor (IL-23R) guide T cells toward the T-helper 17 phenotype. IL-23R single nucleotide polymorphisms (SNPs) have been associated with several autoimmune diseases, including Crohn's disease and rheumatoid arthritis. OBJECTIVE: Our objective was to determine whether variants in the IL-23R gene are associated with Graves' disease (GD) and Graves' ophthalmopathy (GO). DESIGN AND PARTICIPANTS: A total of 216 North American Caucasian GD patients and 368 healthy controls were genotyped for four SNPs spanning the IL-23R gene. SNPs rs11209026 and rs7530511 were genotyped using the TaqMan allelic discrimination assays (Applied Biosystems, Foster City, CA), and SNPs rs2201841 and rs10889677 were genotyped using a fluorescent-based restriction fragment length polymorphism method. RESULTS: The A allele of rs2201841 was present in 78.8% of GD patients with GO and 64.7% of controls [P=1.1x10(-4); odds ratio (OR)=2.04]; the AA genotype was also significantly increased in GO patients compared with controls (62.5 and 41%, respectively; P=1.0x10(-4); OR=2.4). The C allele of rs10889677 was present in 78.6% of GO patients and 64.5% of controls (P=1.3x10(-4); OR=2.03), and the CC genotype was also significantly increased in GO patients vs. controls (62.1 and 41.0%, respectively; P=1.4x10(-4); OR=2.36). The TT genotype of rs7530511 was significantly associated with GD, but not specifically with GO; it was present in 2.5% of GD patients and 0.3% of controls (P=0.02; OR=9.4). The rs11209026 SNP, which is the most strongly associated with Crohn's disease, was not associated with GD or GO in our data set. CONCLUSIONS: Variants in the IL-23R gene are strongly associated with GO. These variants may predispose to GO by changing the expression and/or function of IL-23R, thereby promoting a proinflammatory signaling cascade.

Publication Types:
PMID: 18073300 [PubMed - indexed for MEDLINE]

PMCID: PMC2266952 [Available on 03/01/09]