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

Graham, Jinko ; Kockum, Ingrid ; Sanjeevi, Carani B. ; Landin-Olsson, Mona LU ; Nyström, Lennarth ; Sundkvist, Göran LU ; Arnqvist, Hans ; Blohmé, Göran ; Lithner, Folke and Littorin, Bengt LU , et al. (1999) In European Journal of Immunogenetics 26(2-3). p.117-127
Abstract

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... (More)

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.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
European Journal of Immunogenetics
volume
26
issue
2-3
pages
117 - 127
publisher
Wiley-Blackwell
external identifiers
  • pmid:10331157
  • scopus:0032964464
ISSN
0960-7420
DOI
10.1111/j.1600-0609.2006.00789.x-i1
language
English
LU publication?
yes
id
1d5a84f2-30aa-42db-8247-c22295ca8947
date added to LUP
2019-06-30 23:31:56
date last changed
2024-04-02 11:47:50
@article{1d5a84f2-30aa-42db-8247-c22295ca8947,
  abstract     = {{<p>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.</p>}},
  author       = {{Graham, Jinko and Kockum, Ingrid and Sanjeevi, Carani B. and Landin-Olsson, Mona and Nyström, Lennarth and Sundkvist, Göran and Arnqvist, Hans and Blohmé, Göran and Lithner, Folke and Littorin, Bengt and Scherstén, Bengt and Wibell, Lars and Östman, Jan and Lernmark, Åke and Breslow, Norman and Dahlquist, Gisela}},
  issn         = {{0960-7420}},
  language     = {{eng}},
  month        = {{05}},
  number       = {{2-3}},
  pages        = {{117--127}},
  publisher    = {{Wiley-Blackwell}},
  series       = {{European Journal of Immunogenetics}},
  title        = {{Negative association between type 1 diabetes and HLA DQB1*0602-DQA1*0102 is attenuated with age at onset}},
  url          = {{http://dx.doi.org/10.1111/j.1600-0609.2006.00789.x-i1}},
  doi          = {{10.1111/j.1600-0609.2006.00789.x-i1}},
  volume       = {{26}},
  year         = {{1999}},
}