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Åke Lernmark

Principal investigator

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Negative association between type 1 diabetes and HLA DQB1*0602-DQA1*0102 is attenuated with age at onset

Author

  • Jinko Graham
  • Ingrid Kockum
  • Carani B. Sanjeevi
  • Mona Landin-Olsson
  • Lennarth Nyström
  • Göran Sundkvist
  • Hans Arnqvist
  • Göran Blohmé
  • Folke Lithner
  • Bengt Littorin
  • Bengt Scherstén
  • Lars Wibell
  • Jan Östman
  • Åke Lernmark
  • Norman Breslow
  • Gisela Dahlquist

Summary, in English

HLA-associated relative risks of type 1 (insulin-dependent) diabetes mellitus were analysed in population-based Swedish patients and controls aged 0-34 years. The age dependence of HLA-associated relative risks was assessed by likelihood ratio tests of regression parameters in separate logistic regression models for each HLA category. The analyses demonstrated an attenuation with increasing age at onset in the relative risk for the positively associated DQB1*0201-A1*0502/B1*0302-A1*0301 (DQ2/8) genotype (P = 0.02) and the negatively associated DQB1*0602-A1*0102 (DQ6.2) haplotype (P = 0.004). At birth, DQ6.2-positive individuals had an estimated relative risk of 0.03, but this increased to 1.1 at age 35 years. Relative risks for individuals with DQ genotype 8/8 or 8/X or DQ genotype 2/2 or 2/X, where X is any DQ haplotype ether than 2, 8 or 6.2, were not significantly age-dependent. An exploratory analysis of DQ haplotypes other than 2, 8 and 6.2 suggested that the risk of type 1 diabetes increases with age for DQB1*0604-A1*0102 (DQ6.4) and that the peak risk for the negatively associated DQB1*0301-A1*0501 haplotype is at age 18 years. There was also weak evidence that the risk for DQB1*0303-A1*0301 (DQ9), which has a positive association in the Japanese population, may decrease with age. We speculate that HLA-DQ alleles have a significant effect on the rate of beta cell destruction, which is accelerated in DQ2/8-positive individuals and inhibited, but not completely blocked, in DQ6.2-positive individuals.

Department/s

  • Diabetes lab
  • Medicine, Lund
  • Department of Clinical Sciences, Malmö
  • Family Medicine and Community Medicine

Publishing year

1999-05-05

Language

English

Pages

117-127

Publication/Series

European Journal of Immunogenetics

Volume

26

Issue

2-3

Document type

Journal article

Publisher

Wiley-Blackwell

Topic

  • Endocrinology and Diabetes

Status

Published

Research group

  • Diabetes lab
  • Family Medicine and Community Medicine

ISBN/ISSN/Other

  • ISSN: 0960-7420