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Åke Lernmark

Principal investigator

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HLA Heterozygosity in Insulin‐Dependent Diabetes is Most Frequent at the DQ Locus

Author

  • B. MICHELSEN
  • R. WASSMUTH
  • J. LUDVIGSSON
  • LERNMARK
  • G. T. NEPOM
  • L. FISHER

Summary, in English

Restriction fragment length polymorphism using an HLA‐DQ β‐chain genomic probe showed that 63 children with insulin‐dependent (type 1) diabetes mellitus (IDDM) were all (100%) positive for the BamH1 fragments 12 kb and/or 4 kb compared to 98% (62/63) for HLA‐DR3 and/or 4 and 75% (47/63) for HLA‐B8 and/or 15. The 36 (56%) DR3‐positive children were all 4‐kb‐positive; however, a total of 44 (70%) children were 4‐kb‐positive (P < 0.02). The 55 (87%) DR4‐positive children were all 12‐kb‐positive, but a total of 56 (89%) were 12‐kb‐positive (NS), The heterozygosity at the HLA region increased from 11/63 (18%) for HLA‐B8/15 to 29/63 (46%) for HLA‐DR3/4 (P < 0,0004) and to 37/63 (59%) for the HLA‐DQ 4 kb/12 kb fragments (P < 0.02). The test of an equal probability ofa positive result under the adjacent pair of tests indicates that the increased risk of developing IDDM in association with HLA‐DQ is to a great extent due to heterozygosity at this locus. There were no differences between the 4 kb/12 kb and the DR3/4‐positive IDDM children with respect to fasting or meal‐stimulated C peptide, insulin requirement, or levels of insulin antibodies formed during the first 12 months of insulin therapy. Our results support the hypothesis that HLA‐DQ is closely associated with an increased risk of childhood IDDM, and when typed for at this locus parameters of the clinical course were homogeneous, suggesting that factors other than HLA‐DQ may determine previously observed differences between IDDM children in clinical or functional parameters.

Publishing year

1990-01-01

Language

English

Pages

405-413

Publication/Series

Scandinavian Journal of Immunology

Volume

31

Issue

4

Document type

Journal article

Publisher

Wiley-Blackwell

Status

Published

ISBN/ISSN/Other

  • ISSN: 0300-9475