DR- and DQ-associated protection from Type 1A diabetes : Comparison of DRB11401 and DQA10102-DQB10602

• Published in: The journal of clinical endocrinology and metabolism 2000-10, Vol.85 (10), p.3793-3797
• Main Authors: REDONDO, M. J, KAWASAKI, E, RONNINGEN, K. S, MULGREW, C. L, NOBLE, J. A, ERLICH, H. A, FREED, B. M, LIE, B. A, THORSBY, E, EISENBARTH, G. S, UNDLIEN, D. E
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Cell Line; Diabetes Mellitus, Type 1 - genetics; Diabetes. Impaired glucose tolerance; DNA - genetics; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Genetic Linkage - genetics; Histocompatibility Testing; HLA-DQ alpha-Chains; HLA-DQ Antigens - genetics; HLA-DR Antigens - genetics; HLA-DRB1 Chains; Humans; Medical sciences
• ISSN: 0021-972X
• DOI: 10.1210/jc.85.10.3793

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.