This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Purchase Article View Shopping Cart 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 Imrie, H. Articles by Pearce, S. H. S. Search for Related Content PubMed PubMed Citation Articles by Imrie, H. Articles by Pearce, S. H. S. Pubmed/NCBI databases Gene OMIM UniSTS Substance via MeSH

Evidence for a Graves’ Disease Susceptibility Locus at Chromosome Xp11 in a United Kingdom Population¹

Endocrine Group, Department of Medicine, University of Newcastle upon Tyne (H.I., B.V., P.K.-T., S.H.S.P.), Newcastle upon Tyne, United Kingdom NE2 4HH; Department of Medicine, Freeman Hospital (P.P.), Newcastle upon Tyne, United Kingdom NE7 7DN; Diabetes Care Center, Middlesbrough General Hospital (W.F.K.), Middlesbrough, United Kingdom TS5 5AZ; Endocrine Unit, Royal Infirmary of Edinburgh (A.D.T.), Edinburgh, United Kingdom EH3 9YW; and Department of Medicine, Wansbeck General Hospital (E.T.Y.), Ashington, Northumbria, United Kingdom NE63 9JJ

Address all correspondence and requests for reprints to: Dr. Simon Pearce, Department of Medicine, 4th Floor, Leech Building, The Medical School, University of Newcastle upon Tyne, Newcastle upon Tyne, United Kingdom NE2 4HH. E-mail: spearce{at}hgmp.mrc.ac.uk

Graves’ disease (GD), which has a strong female preponderance (female/male ratio, >5:1), is inherited as a complex genetic trait. Loci for GD have started to be defined using genome-wide approaches for genetic linkage. To date, 3 loci have been confirmed in at least 2 cohorts of GD patients, the strongest effect being at the cytotoxic T lymphocyte antigen-4 (CTLA-4) locus on chromosome 2q33 in our population. Two other loci for GD have recently been proposed, but not confirmed, on chromosomes Xq21 (GD3) and 14q31 (GD1). We studied a cohort of 75 sibling pairs with GD from the United Kingdom for linkage to 12 markers over a 83-cM region of the X chromosome and for 8 markers over a 36-cM region of 14q31-q33. A peak multipoint nonparametric linkage score of 2.21 (P = 0.014) was found at marker DXS8083 on Xp11, which increased to a nonparametric linkage score of 3.18 (P = 0.001) in data that had been conditioned for allele sharing at the CTLA-4 locus under an epistatic model. There was no evidence to support linkage of GD to Xq21.33-q22 (GD3) or at the 14q31-q33 (GD1) region in our population. A locus with a moderate contribution to GD susceptibility (_s = 1.4) is likely to exist in the Xp11 region, but we are unable to confirm that the GD1 or the GD3 regions contain major susceptibility loci in our United Kingdom GD population.

This article has been cited by other articles:

				X. YIN, R. LATIF, Y. TOMER, and T. F. DAVIES Thyroid Epigenetics: X Chromosome Inactivation in Patients with Autoimmune Thyroid Disease Ann. N.Y. Acad. Sci., September 1, 2007; 1110(1): 193 - 200. [Abstract] [Full Text] [PDF]

				G. L. Chen and J. T. Prchal X-linked clonality testing: interpretation and limitations Blood, September 1, 2007; 110(5): 1411 - 1419. [Abstract] [Full Text] [PDF]

				B. Herrera, M. Cader, D. Dyment, J. Bell, G. DeLuca, C. Willer, M. Lincoln, S. Ramagopalan, M. Chao, S-M. Orton, et al. Multiple sclerosis susceptibility and the X chromosome Multiple Sclerosis, August 1, 2007; 13(7): 856 - 864. [Abstract] [PDF]

				C. J Owen, J. A Eden, C. E Jennings, V. Wilson, T. D Cheetham, and S. H S Pearce Genetic association studies of the FOXP3 gene in Graves' disease and autoimmune Addison's disease in the United Kingdom population. J. Mol. Endocrinol., August 1, 2006; 37(1): 97 - 104. [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]

				P. Invernizzi, M. Miozzo, C. Selmi, L. Persani, P. M. Battezzati, M. Zuin, S. Lucchi, P. L. Meroni, B. Marasini, S. Zeni, et al. X Chromosome Monosomy: A Common Mechanism for Autoimmune Diseases J. Immunol., July 1, 2005; 175(1): 575 - 578. [Abstract] [Full Text] [PDF]

				Y.-C. Weng, M.-J. Wu, and W.-S. Lin CT60 Single Nucleotide Polymorphism of the CTLA-4 Gene Is Associated with Susceptibility to Graves' Disease in the Taiwanese Population Ann. Clin. Lab. Sci., January 1, 2005; 35(3): 259 - 264. [Abstract] [Full Text] [PDF]

				Y. Bayer, S. Neumann, B. Meyer, F. Ruschendorf, A. Reske, T. Brix, L. Hegedus, P. Langer, P. Nurnberg, and R. Paschke Genome-Wide Linkage Analysis Reveals Evidence for Four New Susceptibility Loci for Familial Euthyroid Goiter J. Clin. Endocrinol. Metab., August 1, 2004; 89(8): 4044 - 4052. [Abstract] [Full Text] [PDF]

				C. J. Owen, C. E. Jennings, H. Imrie, A. Lachaux, N. A. Bridges, T. D. Cheetham, and S. H. S. Pearce Mutational Analysis of the FOXP3 Gene and Evidence for Genetic Heterogeneity in the Immunodysregulation, Polyendocrinopathy, Enteropathy Syndrome J. Clin. Endocrinol. Metab., December 1, 2003; 88(12): 6034 - 6039. [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]

				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]

				M. Segni, M. A. Pani, A. M. Pasquino, and K. Badenhoop Familial Clustering of Juvenile Thyroid Autoimmunity: Higher Risk Is Conferred by Human Leukocyte Antigen DR3-DQ2 and Thyroid Peroxidase Antibody Status in Fathers J. Clin. Endocrinol. Metab., August 1, 2002; 87(8): 3779 - 3782. [Abstract] [Full Text] [PDF]

				M. A. Pani, K. Regulla, M. Segni, S. Hofmann, M. Hufner, A. M. Pasquino, K.-H. Usadel, and K. Badenhoop A Polymorphism within the Vitamin D-Binding Protein Gene Is Associated with Graves' Disease but Not with Hashimoto's Thyroiditis J. Clin. Endocrinol. Metab., June 1, 2002; 87(6): 2564 - 2567. [Abstract] [Full Text] [PDF]