Journal of Clinical Endocrinology & Metabolism, Vol 79, 227-229, Copyright © 1994 by Endocrine Society

ARTICLES

Strong association between HLA-DQA1*0501 and Graves' disease in a male Caucasian population

T Yanagawa, A Mangklabruks and LJ DeGroot
Department of Medicine, University of Chicago, Illinois 60637.

Graves' disease (GD) is an autoimmune thyroid disease and is associated with human leukocyte antigen (HLA)-DR3 and -DQA1*0501 in caucasians. The incidence of GD is 5 times higher in females than in males, possibly due to their greater immune reactivity. Although many attempts have been made to correlate HLA phenotypes and clinical features of GD little attention has been paid to possible heterogeneous HLA distribution among patients of different sexes. To investigate this possibility, 133 (26 males) unrelated caucasian patients with GD and 104 (43 males) control subjects were typed for HLA-DRB1, -DQA1, and - DQB1, using sequence-specific oligonucleotide probes to analyze polymerase chain reaction-amplified DNA. There were no significant differences in HLA distribution between male and female controls. The frequencies of HLA-DQA1*0501 were increased in both [88.5%; relative risk (RR) = 9.13; P = 0.000015] and female patients (66.4%; RR = 2.66; P = 0.00046) compared to that in the entire control group (42.3%). The frequencies of DR11 (RR = 2.83; P = 0.019) and DQB1*0301 (RR = 2.50; P = 0.034) were increased only in male patients, whereas that of DR3 was higher in female (RR = 2.39; P = 0.0066) and male (RR = 2.54; not significant, P = 0.051) patients, suggesting the possible heterogeneous HLA distribution between the sexes. When the male and female patients were compared, a significant difference was found only for DQA1*0501. The prevalence of DQA1*0501 was significantly higher in males than in females (P = 0.019). As females have augmented immune responsiveness, we speculate that considerable numbers of females may develop GD without a strong HLA susceptibility allele, whereas only a few males develop GD without it.

This article has been cited by other articles:

				S. Rashtak and J. A. Murray Tailored Testing for Celiac Disease Ann Intern Med, September 4, 2007; 147(5): 339 - 341. [Full Text] [PDF]

				A. Rios, J. M. Rodriguez, M. R. Moya, P. J. Galindo, M. Canteras, M. R. Alvarez, and P. Parrilla Associations of HLA-C Alleles With Multinodular Goiters: Study in a Population From Southeastern Spain. Arch Surg, February 1, 2006; 141(2): 123 - 128. [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]

				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]

				Y. Jin, W. Teng, S. Ben, X. Xiong, J. Zhang, S. Xu, Y. Y. Shugart, L. Jin, J. Chen, and W. Huang Genome-Wide Scan of Graves' Disease: Evidence for Linkage on Chromosome 5q31 in Chinese Han Pedigrees J. Clin. Endocrinol. Metab., April 1, 2003; 88(4): 1798 - 1803. [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]

				Q.-Y. Chen, D. Nadell, X.-Y. Zhang, A. Kukreja, Y.-J. Huang, J. Wise, F. Svec, R. Richards, K. E. Friday, A. Vargas, et al. The Human Leukocyte Antigen HLA DRB3*0202/DQA1*0501 Haplotype Is Associated with Graves' Disease in African Americans J. Clin. Endocrinol. Metab., April 1, 2000; 85(4): 1545 - 1549. [Abstract] [Full Text]

				Q.-Y. Chen, W. Huang, J.-X. She, F. Baxter, R. Volpe, and N. K. Maclaren HLA-DRB108, DRB103/DRB30101, and DRB30202 Are Susceptibility Genes for Graves' Disease in North American Caucasians, Whereas DRB107 Is Protective J. Clin. Endocrinol. Metab., September 1, 1999; 84(9): 3182 - 3186. [Abstract] [Full Text]

				T. F. Davies Autoimmune Thyroid Disease Genes Come in Many Styles and Colors J. Clin. Endocrinol. Metab., October 1, 1998; 83(10): 3391 - 3393. [Full Text]