This Article 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 Tomer, Y. Articles by Davies, T. F. Search for Related Content PubMed PubMed Citation Articles by Tomer, Y. Articles by Davies, T. F.

Thyroglobulin Is a Thyroid Specific Gene for the Familial Autoimmune Thyroid Diseases

Division of Endocrinology, Diabetes and Bone Diseases, Department of Medicine (Y.T., E.C., Y.B., T.F.D.), and Departments of Psychiatry and Biomathematics (D.A.D.), Mount Sinai School of Medicine, New York, New York 10029

The autoimmune thyroid diseases (AITDs) develop as a result of a complex interaction between predisposing genes and non-genetic factors. We have completed a whole genome scan in 56 families which revealed 7 major AITD loci (LOD scores >2), and additional minor loci (LOD scores >1). One of the minor loci was on chromosome 8q24 giving a maximum LOD score (MLS) of 1.8 at marker D8S284. This locus contained the thyroglobulin (Tg) gene which was a strong candidate gene for AITD. Because of this we analyzed the Tg gene region in detail using an expanded dataset of 102 families. The new linkage analysis showed stronger evidence for linkage at the Tg gene locus with an MLS of 3.5 between markers D8S514 and D8S284 (NPL = 2.0). We then proceeded to analyze the Tg gene directly. We identified a new microsatellite inside intron 27 of the Tg gene (designated Tgms2). Tgms2 showed strong evidence for linkage with AITD (MLS = 2.9), further suggesting that the Tg gene was linked to AITD. Association studies comparing 224 Caucasian AITD patients to 134 Caucasian controls showed an association of Tgms2 with AITD (p = 0.05, relative risk [RR] = 1.4). The association was stronger when only the probands from the linked families (n = 32) were used (p = 0.004, RR = 2.3). Transmission disequilibrium test (TDT) analysis also showed an association of Tgms2 with AITD (p = 0.02). We concluded therefore that the Tg gene was a major AITD susceptibility gene because it was both linked and associated with AITD.

This article has been cited by other articles:

				H. He, R. Nagy, S. Liyanarachchi, H. Jiao, W. Li, S. Suster, J. Kere, and A. de la Chapelle A Susceptibility Locus for Papillary Thyroid Carcinoma on Chromosome 8q24 Cancer Res., January 15, 2009; 69(2): 625 - 631. [Abstract] [Full Text] [PDF]

				M. S. Anderson Update in Endocrine Autoimmunity J. Clin. Endocrinol. Metab., October 1, 2008; 93(10): 3663 - 3670. [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]

				Y. Ban, D. A. Greenberg, T. F. Davies, E. Jacobson, E. Concepcion, and Y. Tomer 'Linkage Analysis of Thyroid Antibody Production: Evidence for Shared Susceptibility to Clinical Autoimmune Thyroid Disease J. Clin. Endocrinol. Metab., September 1, 2008; 93(9): 3589 - 3596. [Abstract] [Full Text] [PDF]

				K. K. L. Chong, S. W. Y. Chiang, G. W. K. Wong, P. O. S. Tam, T.-K. Ng, Y.-J. Hu, G. H. F. Yam, D. S. C. Lam, and C.-P. Pang Association of CTLA-4 and IL-13 Gene Polymorphisms with Graves' Disease and Ophthalmopathy in Chinese Children Invest. Ophthalmol. Vis. Sci., June 1, 2008; 49(6): 2409 - 2415. [Abstract] [Full Text] [PDF]

				M. Caputo, C. M Rivolta, V. J Gutnisky, L. Gruneiro-Papendieck, A. Chiesa, G. Medeiros-Neto, R. Gonzalez-Sarmiento, and H. M Targovnik Recurrence of the p.R277X/p.R1511X compound heterozygous mutation in the thyroglobulin gene in unrelated families with congenital goiter and hypothyroidism: haplotype analysis using intragenic thyroglobulin polymorphisms J. Endocrinol., October 1, 2007; 195(1): 167 - 177. [Abstract] [Full Text] [PDF]

				J.-Y. Hsiao, M.-C. Hsieh, K.-J. Tien, S.-C. Hsu, S.-J. Shin, and S.-R. Lin Association between a C/T Polymorphism in Exon 33 of the Thyroglobulin Gene Is Associated with Relapse of Graves' Hyperthyroidism after Antithyroid Withdrawal in Taiwanese J. Clin. Endocrinol. Metab., August 1, 2007; 92(8): 3197 - 3201. [Abstract] [Full Text] [PDF]

				T. F. Davies Editorial: X versus X--The Fight for Function within the Female Cell and the Development of Autoimmune Thyroid Disease J. Clin. Endocrinol. Metab., November 1, 2005; 90(11): 6332 - 6333. [Full Text] [PDF]

				B. Golden, L. Levin, Y. Ban, E. Concepcion, D. A. Greenberg, and Y. Tomer Genetic Analysis of Families with Autoimmune Diabetes and Thyroiditis: Evidence for Common and Unique Genes J. Clin. Endocrinol. Metab., August 1, 2005; 90(8): 4904 - 4911. [Abstract] [Full Text] [PDF]

				C. M. Rivolta, C. M. Moya, V. J. Gutnisky, V. Varela, J. M. Miralles-Garcia, R. Gonzalez-Sarmiento, and H. M. Targovnik A New Case of Congenital Goiter with Hypothyroidism Caused by a Homozygous p.R277X Mutation in the Exon 7 of the Thyroglobulin Gene: A Mutational Hot Spot Could Explain the Recurrence of This Mutation J. Clin. Endocrinol. Metab., June 1, 2005; 90(6): 3766 - 3770. [Abstract] [Full Text] [PDF]

				J. E. Collins, J. M. Heward, J. M. M. Howson, H. Foxall, J. Carr-Smith, J. A. Franklyn, and S. C. L. Gough Common Allelic Variants of Exons 10, 12, and 33 of the Thyroglobulin Gene Are Not Associated with Autoimmune Thyroid Disease in the United Kingdom J. Clin. Endocrinol. Metab., December 1, 2004; 89(12): 6336 - 6339. [Abstract] [Full Text] [PDF]

				S. Shirasawa, H. Harada, K. Furugaki, T. Akamizu, N. Ishikawa, K. Ito, K. Ito, H. Tamai, K. Kuma, S. Kubota, et al. SNPs in the promoter of a B cell-specific antisense transcript, SAS-ZFAT, determine susceptibility to autoimmune thyroid disease Hum. Mol. Genet., October 1, 2004; 13(19): 2221 - 2231. [Abstract] [Full Text] [PDF]

				Y. Ban, D. A. Greenberg, E. Concepcion, L. Skrabanek, R. Villanueva, and Y. Tomer Amino acid substitutions in the thyroglobulin gene are associated with susceptibility to human and murine autoimmune thyroid disease PNAS, December 9, 2003; 100(25): 15119 - 15124. [Abstract] [Full Text] [PDF]

				Y. Tomer and T. F. Davies Searching for the Autoimmune Thyroid Disease Susceptibility Genes: From Gene Mapping to Gene Function Endocr. Rev., October 1, 2003; 24(5): 694 - 717. [Abstract] [Full Text] [PDF]

				J. E. Collins, J. M. Heward, J. Carr-Smith, J. Daykin, J. A. Franklyn, and S. C. L. Gough Association of a Rare Thyroglobulin Gene Microsatellite Variant with Autoimmune Thyroid Disease J. Clin. Endocrinol. Metab., October 1, 2003; 88(10): 5039 - 5042. [Abstract] [Full Text] [PDF]

				H. H. Kacem, A. Rebai, N. Kaffel, S. Masmoudi, M. Abid, and H. Ayadi PDS Is a New Susceptibility Gene to Autoimmune Thyroid Diseases: Association and Linkage Study J. Clin. Endocrinol. Metab., May 1, 2003; 88(5): 2274 - 2280. [Abstract] [Full Text] [PDF]

				S. P. Hamilton, A. J. Fyer, M. Durner, G. A. Heiman, A. Baisre de Leon, S. E. Hodge, J. A. Knowles, and M. M. Weissman Further genetic evidence for a panic disorder syndrome mapping to chromosome 13q PNAS, March 4, 2003; 100(5): 2550 - 2555. [Abstract] [Full Text] [PDF]

				F. Latrofa, P. Pichurin, J. Guo, B. Rapoport, and S. M. McLachlan Thyroglobulin-Thyroperoxidase Autoantibodies Are Polyreactive, Not Bispecific: Analysis Using Human Monoclonal Autoantibodies J. Clin. Endocrinol. Metab., January 1, 2003; 88(1): 371 - 378. [Abstract] [Full Text] [PDF]

				B. Vaidya, P. Kendall-Taylor, and S. H. S. Pearce The Genetics of Autoimmune Thyroid Disease J. Clin. Endocrinol. Metab., December 1, 2002; 87(12): 5385 - 5397. [Full Text] [PDF]