Negative association between type 1 diabetes and HLA DQB1*0602-DQA1*0102 is attenuated with age at onset
(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.
(Less)
- author
- organization
- publishing date
- 1999-05-05
- 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
- 2024-07-09 22:09:01
@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}}, }