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The Human Leukocyte Antigen HLA DRB3_*0202/DQA1_*0501 Haplotype Is Associated with Graves’ Disease in African Americans

The Research Institute for Children (Q.-Y.C., D.N., X.-Y.Z., A.K., Y.-J.H., A.V., R.G., S.C., M.L., N.K.M.), Children’s Hospital, Harahan, Louisiana 70123; Departments of Pediatrics (Q.-Y.C., A.K., A.V., R.G., S.C., M.S.L., N.K.M.) and Medicine (F.S.), LSUMS, New Orleans, Louisiana 70112; Institute for the Treatment of Diabetes and Metabolism (J.W.), Methodist Hospital, New Orleans, Louisiana 70127; Department of Medicine (R.R., K.E.F.), Tulane University Medical Center, New Orleans, Louisiana 70112; and Division of Endocrinology and Metabolism (Y.T.), Mount Sinai School of Medicine, New York, New York 10029

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

Information on genetic susceptibility to Graves’ disease in African Americans is limited. We studied DRB1, DQB1, DRB3 subtypes, DQA1_*0501, DQA1_*0201, and CTLA-4 polymorphisms in 49 African American patients with adult onset Graves’ disease and 47 racially-matched controls using PCR-based sequence-specific priming methods. There were no significant differences in DRB1 or DQB1 allelic frequencies or CTLA-4 polymorphisms between patients and controls. However, we found that the frequency of DRB3 was significantly increased in the patients (75.5% vs. 57.4%, P = 0.006, X² = 3.52), especially for the DRB3_*0202 subtype (53.1% vs. 23.4, P = 0.003, X² = 8.91). In this one respect, the finding was in concordance with our previous observations in Caucasian patients with adult-onset Graves’ disease. In addition, whereas the frequency of DQA1_*0501 was increased (P = 0.018, X² = 5.63) in our patients, the haplotype of DRB3/DQA1_*0501, or DRB3_*0202/DQA1_*0501 was found to be more strongly associated (P = 0.008, X² = 7.0; P = 0.0008, X² = 11.34, respectively). These data suggest that DRB3_*0202, particularly when found with DQA1_*0501 in a haplotype is a susceptible gene(s) for Graves’ disease in adult African Americans. Considering these data with those in Caucasian patients, our results would suggest that the primary Graves susceptible locus is likely DRB3 and not DRB1.

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