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

Sanjeevi, C. B. ; Höök, P. ; Landin-Olsson, M. LU ; Kockum, I. ; Dahlquist, G. ; Lybrand, T. P. and Lernmark, Å LU orcid (1996) In Tissue Antigens 47(4). p.275-283
Abstract

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... (More)

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.

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author
; ; ; ; ; and
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Genetic susceptibility, HLA-DQ, HLA-DR, IDDM
in
Tissue Antigens
volume
47
issue
4
pages
275 - 283
publisher
Wiley-Blackwell
external identifiers
  • scopus:0029968375
  • pmid:8773316
ISSN
0001-2815
DOI
10.1111/j.1399-0039.1996.tb02554.x
language
English
LU publication?
no
id
15850a34-b9f9-400c-8f8b-00fed45f4043
date added to LUP
2019-07-01 13:24:09
date last changed
2024-03-13 08:25:29
@article{15850a34-b9f9-400c-8f8b-00fed45f4043,
  abstract     = {{<p>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 &lt; 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 &lt; 0.01) and (*)0404 (16% patients and 10% controls; OR 1.67, p &lt; 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 &lt; 0.01; 15% patients and 10% controls; OR 1.55, p &lt; 0.05, respectively). When DRB1(*)0401 was linked to DQB1(*)0301-DQA1(*)0301 (DQ7) (6% patients and 11% controls; OR 0.52, p &lt; 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) &gt; DQB1(*)0302 &gt; DRB1(*)0401 &gt; 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.</p>}},
  author       = {{Sanjeevi, C. B. and Höök, P. and Landin-Olsson, M. and Kockum, I. and Dahlquist, G. and Lybrand, T. P. and Lernmark, Å}},
  issn         = {{0001-2815}},
  keywords     = {{Genetic susceptibility; HLA-DQ; HLA-DR; IDDM}},
  language     = {{eng}},
  month        = {{01}},
  number       = {{4}},
  pages        = {{275--283}},
  publisher    = {{Wiley-Blackwell}},
  series       = {{Tissue Antigens}},
  title        = {{DR4 subtypes and their molecular properties in a population-based study of Swedish childhood diabetes}},
  url          = {{http://dx.doi.org/10.1111/j.1399-0039.1996.tb02554.x}},
  doi          = {{10.1111/j.1399-0039.1996.tb02554.x}},
  volume       = {{47}},
  year         = {{1996}},
}