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Åke Lernmark

Principal investigator

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DR4 subtypes and their molecular properties in a population-based study of Swedish childhood diabetes

Author

  • C. B. Sanjeevi
  • P. Höök
  • M. Landin-Olsson
  • I. Kockum
  • G. Dahlquist
  • T. P. Lybrand
  • Å Lernmark

Summary, in English

The aim of this study was to determine the association between childhood insulin-dependent diabetes mellitus (IDDM) and HLA-DR4 subtypes and to test in a population-based investigation whether the DR4 association has an effect independent to that of DQ. First, HLA genotyping identified DR4 in 337/425 (79%) patients and 148/367 (40%) controls (Odds Ratio 5.67; p < 0.01). Second, a total of 14 DR4 subtypes were detected by PCR and sequence specific oligo probes. Only two DR4 subtypes, DRB1(*)0401 (62% patients and 25% controls; OR 4.95, p < 0.01) and (*)0404 (16% patients and 10% controls; OR 1.67, p < 0.05) were however positively associated with the disease. These two subtypes were positively associated only when linked to DQB1(*)0302-DQA1(*)0301 (DQ8) (56% patients and 14% controls; OR 7.69, p < 0.01; 15% patients and 10% controls; OR 1.55, p < 0.05, respectively). When DRB1(*)0401 was linked to DQB1(*)0301-DQA1(*)0301 (DQ7) (6% patients and 11% controls; OR 0.52, p < 0.05), this DR4 subtypes was negatively associated with IDDM. Third, tests of strongest association allowed the following ranking of alleles or haplotypes: DQB1(*)0302-DQA1(*)0301 (DQ8) > DQB1(*)0302 > DRB1(*)0401 > DRB1(*)0404 and the association of DRB1(*)0401 has a significant effect in DQ8 positive IDDM patients. We conclude that the DR4 association with IDDM is secondary to DQ by linkage disequilibrium, which support the role of HLA-DQ as a primary genetic risk factor for IDDM.

Publishing year

1996-01-01

Language

English

Pages

275-283

Publication/Series

Tissue Antigens

Volume

47

Issue

4

Document type

Journal article

Publisher

Wiley-Blackwell

Topic

  • Endocrinology and Diabetes

Keywords

  • Genetic susceptibility
  • HLA-DQ
  • HLA-DR
  • IDDM

Status

Published

ISBN/ISSN/Other

  • ISSN: 0001-2815