DR- and DQ-Associated Protection from Type 1A Diabetes
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Posted by Sarah on 18:54:14 2006/07/11
In Reply to:
Genetic Mutation Found That Is Major Contributor To Type 1 Diabetes posted by Sarah
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Original Studies
DR- and DQ-Associated Protection from Type 1A Diabetes: Comparison of DRB111401 and DQA1,10102-DQB1,10602,1
M. J. Redondo, E. Kawasaki, C. L. Mulgrew, J. A. Noble, H. A. Erlich, B. M. Freed, B. A. Lie, E. Thorsby, G. S. Eisenbarth, D. E. Undlien and K. S. Ronningen
Barbara Davis Center for Childhood Diabetes (M.J.R., E.K., C.L.M., G.S.E.) and Department of Medicine (B.M.F.), University of Colorado Health Sciences Center, Denver, Colorado 80262; Children's Hospital Oakland Research Institute (J.A.N., H.A.E.), Oakland, California 94609; Department of Human Genetics, Inc. (J.A.N., H.A.E.), Roche Molecular Systems, Alameda, California 94501; Institute of Immunology (B.A.L., E.T., D.E.U.), The National Hospital, University of Oslo, 0027 Oslo, Norway; and Section of Epidemiology (K.S.R.), National Institute of Public Health, N-0403 Oslo, Norway
Address correspondence and requests for reprints to: George S. Eisenbarth, M.D., Ph.D., Barbara Davis Center for Childhood Diabetes, University of Colorado Health Sciences Center, 4200 East 9th Avenue, B-140, Denver, Colorado 80262. E-mail: george.eisenbarth@UCHSC.edu.
The transmission disequilibrium test was used to analyze haplotypes for association and linkage to diabetes within families from the Human Biological Data Interchange type 1 diabetes repository (n = 1371 subjects) and from the Norwegian Type 1 Diabetes Simplex Families study (n = 2441 subjects). DQA1*0102-DQB1*0602 was transmitted to 2 of 313 (0.6%) affected offspring (P < 0.001, vs. the expected 50% transmission). Protection was associated with the DQ alleles rather than DRB1*1501 in linkage disequilibrium with DQA1*0102-DQB1*0602: rare DRB1*1501 haplotypes without DQA1*0102-DQB1*0602 were transmitted to 5 of 11 affected offspring, whereas DQA1*0102-DQB1*0602 was transmitted to 2 of 313 affected offspring (P < 0.0001). Rare DQA1*0102-DQB1*0602 haplotypes without DRB1*1501 were never transmitted to affected offspring (n = 6).
The DQA1*0101-DQB1*0503 haplotype was transmitted to 2 of 42 (4.8%) affected offspring (P < 0.001, vs. 50% expected transmission). Although DRB1*1401 is in linkage disequilibrium with DQB1*0503, neither of the two affected children who carried DQA1*0101-DQB1*0503 had DRB1*1401. However, all 13 nonaffected children who inherited DQA1*0101-DQB1*0503 had DRB1*1401. In a case-control comparison of patients from the Barbara Davis Center, DQA1*0101-DQB1*0503 was found in 5 of 110 (4.5%) controls compared with 3 of 728 (0.4%) patients (P < 0.005). Of the three patients with DQB1*0503, only one had DRB1*1401. Our data suggest that both DR and DQ molecules (the DRB1*1401 and DQA1*0102-DQB1*0602 alleles) can provide protection from type 1A diabetes.
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