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 Chen, Q.-Y. Articles by Maclaren, N. K. Search for Related Content PubMed PubMed Citation Articles by Chen, Q.-Y. Articles by Maclaren, N. K.

HLA-DRB1¹08, DRB1^,103/DRB3^,10101, and DRB3^,10202 Are Susceptibility Genes for Graves’ Disease in North American Caucasians, Whereas DRB1^,107 Is Protective^,1

The Research Institute for Children (Q.-Y.C., N.K.M.), Harahan, Louisiana 70123; Children’s Hospital (Q.-Y.C., N.K.M.); and the Department of Pediatrics, Louisiana State University Medical Center (Q.-Y.C., N.K.M.), New Orleans, Louisiana 70112; the Department of Pathology and Laboratory Medicine, University of Florida College of Medicine (W.H., J.-X.S., F.B.), Gainesville, Florida 32610; and the Division of Endocrinology, Department of Medicine, University of Toronto (R.V.), Toronto, Canada

Address all correspondence and requests for reprints to: Noel K. Maclaren, M.D., Research Institute for Children, 520 Elmwood Park Boulevard, Suite 160, Harahan, Louisiana 70123. E-mail: nkmaclaren{at}aol.com

Graves’ disease is known to be HLA-D associated; however, the primary loci involved remain unclear. We examined HLA genotypes of DRB1 and DQB1 plus DRB3 subtypes using PCR-based sequence-specific priming in two groups of North American (Gainesville, FL; and Toronto, Canada) Caucasian patients with Graves’ disease. We stratified patients into those with either early age at onset (<20 yr; 13.1 ± 4.8 yr; n = 30) and later age at onset of disease (38.8 ± 9.7 yr; n = 62) and compared the results to 192 normal controls. As expected, we found that DRB1*03 was associated with Graves’ disease, but at a higher odds ratios for early-onset than later-onset patients (3.7 vs. 2.2). The frequency of DRB1*08 was also increased in both groups of patients, but significantly so only in patients with early-onset Graves’ (P = 0.001; ² = 10.8). DRB3 was highly associated with Graves’ in both groups of patients (P = 0.009; ² = 6.83 and P = 0.0015; ² = 10.1, respectively); however, the subtypes of DRB3 revealed differential susceptibilities. Whereas the frequencies of both DRB3*0101 and DRB3*0202 were increased over the entire cohort, that of DRB3*0301 was not. Significant P values were found for DRB3*0101 in patients with early-onset and for DRB3*0202 in patients with later onset of Graves’ disease. When the haplotypes of DRB1*03-DRB3 of all subtypes were removed for analysis (all DRB1*03 positive also had DRB3*0101), the frequency of DRB3*0202 remained significantly higher in the patients with later onset of Graves’ disease than in controls (P = 0.0043; ² = 8.13), but DRB3 was no longer positively associated with the early-onset group. In addition, we found that DRB1*07 was negatively associated with both groups of patients (P = 0.024; ² = 5.10 and P = 0.0085; ² = 6.93). These data suggest that DRB3*0202 is more likely to be the primary susceptible locus than DRB1*03 for patients with later onset of Graves’ disease.

This article has been cited by other articles:

				G. Bioley, C. Dousset, A. Yeh, B. Dupont, N. Bhardwaj, G. Mears, L. J. Old, M. Ayyoub, and D. Valmori Vaccination with Recombinant NY-ESO-1 Protein Elicits Immunodominant HLA-DR52b-restricted CD4+ T Cell Responses with a Conserved T Cell Receptor Repertoire Clin. Cancer Res., July 1, 2009; 15(13): 4467 - 4474. [Abstract] [Full Text] [PDF]

				J.-Y. Hsiao, M.-C. Hsieh, C.-T. Hsiao, H.-H. Weng, and D.-S. Ke Association of CD40 and thyroglobulin genes with later-onset Graves' disease in Taiwanese patients Eur. J. Endocrinol., November 1, 2008; 159(5): 617 - 621. [Abstract] [Full Text] [PDF]

				S. Dai, F. Crawford, P. Marrack, and J. W. Kappler The structure of HLA-DR52c: Comparison to other HLA-DRB3 alleles PNAS, August 19, 2008; 105(33): 11893 - 11897. [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]

				H. Inaba, W. Martin, A. S. De Groot, S. Qin, and L. J. De Groot Thyrotropin Receptor Epitopes and Their Relation to Histocompatibility Leukocyte Antigen-DR Molecules in Graves' Disease J. Clin. Endocrinol. Metab., June 1, 2006; 91(6): 2286 - 2294. [Abstract] [Full Text] [PDF]

				B. S. Prabhakar, R. S. Bahn, and T. J. Smith Current Perspective on the Pathogenesis of Graves' Disease and Ophthalmopathy Endocr. Rev., December 1, 2003; 24(6): 802 - 835. [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]

				A. Alkhateeb, G. L. Stetler, W. Old, J. Talbert, C. Uhlhorn, M. Taylor, A. Fox, C. Miller, D. G. Dills, E. C. Ridgway, et al. Mapping of an autoimmunity susceptibility locus (AIS1) to chromosome 1p31.3-p32.2 Hum. Mol. Genet., March 1, 2002; 11(6): 661 - 667. [Abstract] [Full Text] [PDF]

				A. P. Weetman Graves' Disease N. Engl. J. Med., October 26, 2000; 343(17): 1236 - 1248. [Full Text] [PDF]

				N. C. Lambert, P. C. Evans, T. L. Hashizumi, S. Maloney, T. Gooley, D. E. Furst, and J. L. Nelson Cutting Edge: Persistent Fetal Microchimerism in T Lymphocytes Is Associated with HLA-DQA1*0501: Implications in Autoimmunity J. Immunol., June 1, 2000; 164(11): 5545 - 5548. [Abstract] [Full Text] [PDF]