This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hiratani, H. Articles by Akamizu, T. Search for Related Content PubMed PubMed Citation Articles by Hiratani, H. Articles by Akamizu, T. Related Collections Thyroid

Multiple SNPs in Intron 7 of Thyrotropin Receptor Are Associated with Graves’ Disease

Department of Experimental Therapeutics (H.H., S.I., A.S., T.A.), Translational Research Center, Kyoto University Hospital, Kyoto University School of Medicine, Kyoto 606-8507, Japan; Department of Clinical Laboratory Science (H.H., Y.I.), School of Allied Health Science, Osaka University, Osaka 565-0871, Japan; Department of Pathology (S.S.), International Medical Center of Japan, Tokyo 162-8655, Japan; and Department of Biochemistry (D.W.B.), Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157

Address all correspondence and requests for reprints to: Takashi Akamizu, Translational Research Center, Kyoto University Hospital, 54 Shogoin-Kawaharacho, Sakyo-ku, Kyoto 606-8507, Japan. E-mail: akamizu{at}kuhp.kyoto-u.ac.jp.

Our previous studies using microsatellite markers near or in the TSH receptor (TSHR) gene revealed significant association between autoimmune thyroid disease (AITD) in Japanese patients and TSHR microsatellite alleles. In the present study, we performed a case-control analysis of AITD using single-nucleotide polymorphisms (SNPs) spaced 3–50 kb apart spanning the TSHR gene. We observed significant associations between AITD/Graves’ disease (GD)/Hashimoto’s thyroiditis and multiple SNPs. Specifically, the SNP JST022302 and several adjacent SNPs in intron 7 of the TSHR gene were significantly associated with GD (P = 0.039–0.0004) but not Hashimoto’s thyroiditis. Furthermore, we identified three haplotype blocks around intron 7 by linkage disequilibrium analysis. A single SNP haplotype [AATG(CT)₆(TT)AG] in the haplotype block including JST022302 showed significant association with GD in haplotype case-control analysis (P = 0.0058). These findings suggest that alleles of intron 7 of the TSHR gene contribute to GD susceptibility.

This article has been cited by other articles:

				O. J. Brand, J. C. Barrett, M. J. Simmonds, P. R. Newby, C. J. McCabe, C. K. Bruce, B. Kysela, J. D. Carr-Smith, T. Brix, P. J. Hunt, et al. Association of the thyroid stimulating hormone receptor gene (TSHR) with Graves' disease Hum. Mol. Genet., May 1, 2009; 18(9): 1704 - 1713. [Abstract] [Full Text] [PDF]

				H.-D. Song, J. Liang, J.-Y. Shi, S.-X. Zhao, Z. Liu, J.-J. Zhao, Y.-D. Peng, G.-Q. Gao, J. Tao, C.-M. Pan, et al. Functional SNPs in the SCGB3A2 promoter are associated with susceptibility to Graves' disease Hum. Mol. Genet., March 15, 2009; 18(6): 1156 - 1170. [Abstract] [Full Text] [PDF]

				A. Huber, F. Menconi, S. Corathers, E. M. Jacobson, and Y. Tomer Joint Genetic Susceptibility to Type 1 Diabetes and Autoimmune Thyroiditis: from Epidemiology to Mechanisms Endocr. Rev., October 1, 2008; 29(6): 697 - 725. [Abstract] [Full Text] [PDF]

				A. Sutherland, J. Davies, C. J. Owen, S. Vaikkakara, C. Walker, T. D. Cheetham, R. A. James, P. Perros, P. T. Donaldson, H. J. Cordell, et al. Genomic Polymorphism at the Interferon-Induced Helicase (IFIH1) Locus Contributes to Graves' Disease Susceptibility J. Clin. Endocrinol. Metab., August 1, 2007; 92(8): 3338 - 3341. [Abstract] [Full Text] [PDF]

				C. J. Owen, H. Kelly, J. A. Eden, M. E. Merriman, S. H. S. Pearce, and T. R. Merriman Analysis of the Fc Receptor-Like-3 (FCRL3) Locus in Caucasians with Autoimmune Disorders Suggests a Complex Pattern of Disease Association J. Clin. Endocrinol. Metab., March 1, 2007; 92(3): 1106 - 1111. [Abstract] [Full Text] [PDF]

				R. P Peeters, W. M van der Deure, and T. J Visser Genetic variation in thyroid hormone pathway genes; polymorphisms in the TSH receptor and the iodothyronine deiodinases. Eur. J. Endocrinol., November 1, 2006; 155(5): 655 - 662. [Abstract] [Full Text] [PDF]

				H. A. Aliesky, P. N. Pichurin, C.-R. Chen, R. W. Williams, B. Rapoport, and S. M. McLachlan Probing the Genetic Basis for Thyrotropin Receptor Antibodies and Hyperthyroidism in Immunized CXB Recombinant Inbred Mice Endocrinology, June 1, 2006; 147(6): 2789 - 2800. [Abstract] [Full Text] [PDF]