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Islet Cell Antibody-Positive Relatives with Human Leukocyte Antigen DQA1¹0102, DQB1^,10602: Identification by the Diabetes Prevention Trial-Type 1^,1

Department of Veterans Affairs, Puget Sound Health Care System, and the Department of Medicine, University of Washington (C.J.G.), Seattle, Washington 98108; Department of Pediatrics, University of Florida (D.A.S.), Gainesville, Florida 32610; H. Lee Moffitt Cancer Center and Research Institute, University of South Florida (D.C., J.P.K.), Tampa, Florida 33612; Barbara Davis Center for Childhood Diabetes, University of Colorado (G.S.E.), Denver, Colorado 80262; and Department of Medicine, Endocrinology, and Diabetes, University of Southern California (A.Z.), Los Angeles, California 90033.

Address all correspondence and requests for reprints to: Dr. Carla J. Greenbaum, Department of Veterans Affairs, Puget Sound Health Care System, and the Department of Medicine, University of Washington, Seattle, Washington 98108.

The presence of human leukocyte antigen (HLA) haplotype DQA1*0102, DQB1*0602 is associated with protection from type 1 diabetes. The Diabetes Prevention Trial-type 1 has identified 100 islet cell antibody (ICA)-positive relatives with this protective haplotype, far exceeding the number of such subjects reported in other studies worldwide. Comparisons between ICA⁺ relatives with and without DQB1*0602 demonstrated no differences in gender or age; however, among racial groups, African-American ICA⁺ relatives were more likely to carry this haplotype than others. The ICA⁺ DQB1*0602 individuals were less likely to have additional risk factors for diabetes [insulin autoantibody (IAA) positive or low first phase insulin release (FPIR)] than ICA⁺ relatives without DQB1*0602. However, 29% of the ICA⁺ DQB1*0602 relatives did have IAA or low FPIR. Although half of the ICA⁺ DQB1*0602 relatives had a high risk second haplotype, this was not associated with the additional risk factors for diabetes. Hispanic ICA⁺ individuals with DQB1*0602 were more likely to be IAA positive or to have low FPIR than other racial groups. In conclusion, the presence of ICA in the relatives described here suggests that whatever the mechanism that protects DQB1*0602 individuals from diabetes, it is likely to occur after the diabetes disease process has begun. In addition, there may be different effects of DQB1*0602 between ethnic groups.

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