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Multiple Loci in the HLA Complex Are Associated with Addison's Disease.

Skinningsrud, Beate; Lie, Benedicte A; Lavant, Ewa; Carlson, Joyce LU ; Erlich, Henry; Akselsen, Hanne E; Gervin, Kristina; Wolff, Anette B; Erichsen, Martina M and Lövås, Kristian, et al. (2011) In The Journal of clinical endocrinology and metabolism 96. p.1703-1708
Abstract
Context: A strong association between autoimmune Addison's disease (AAD) and major histocompatibility complex class II-encoded HLA-DRB1-DQA1-DQB1 haplotypes is well known. Recent evidence from other autoimmune diseases has suggested that class I-encoded HLA-A and HLA-B gene variants confer HLA-DRB1-DQA1-DQB1-independent effects on disease. Objective: We aimed to explore AAD predisposing effects of HLA-A and -B and further investigate the role of MICA and HLA-DRB1-DQA1-DQB1 in a much larger material than has previously been studied. Design: HLA-A, -B, -DRB1, and -DQB1 and a microsatellite in MICA were genotyped in 414 AAD patients and 684 controls of Norwegian origin. Results: The strongest association was observed for the DRB1 locus, in... (More)
Context: A strong association between autoimmune Addison's disease (AAD) and major histocompatibility complex class II-encoded HLA-DRB1-DQA1-DQB1 haplotypes is well known. Recent evidence from other autoimmune diseases has suggested that class I-encoded HLA-A and HLA-B gene variants confer HLA-DRB1-DQA1-DQB1-independent effects on disease. Objective: We aimed to explore AAD predisposing effects of HLA-A and -B and further investigate the role of MICA and HLA-DRB1-DQA1-DQB1 in a much larger material than has previously been studied. Design: HLA-A, -B, -DRB1, and -DQB1 and a microsatellite in MICA were genotyped in 414 AAD patients and 684 controls of Norwegian origin. Results: The strongest association was observed for the DRB1 locus, in which the DRB1*03:01 and DRB1*04:04 conferred increased risk of AAD, particularly in a heterozygous combination [odds ratio 22.13; 95% confidence interval (11.39-43.98); P = 6 × 10(-20)]. After conditioning on DRB1, association with AAD was still present for HLA-B and MICA, suggesting the presence of additional risk factors. Conclusions: The major histocompatibility complex harbors multiple risk loci for AAD, in which DRB1 appears to represent the main risk factor. (Less)
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Contribution to journal
publication status
published
subject
in
The Journal of clinical endocrinology and metabolism
volume
96
pages
1703 - 1708
publisher
The Endocrine Society
external identifiers
  • WOS:000295879600022
  • PMID:21816777
  • Scopus:80053470015
ISSN
1945-7197
DOI
10.1210/jc.2011-0645
language
English
LU publication?
yes
id
36ef4a0a-db54-40ed-b6f5-e63d18eabcf9 (old id 2151424)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/21816777?dopt=Abstract
date added to LUP
2011-09-04 16:11:28
date last changed
2016-12-04 04:40:09
@misc{36ef4a0a-db54-40ed-b6f5-e63d18eabcf9,
  abstract     = {Context: A strong association between autoimmune Addison's disease (AAD) and major histocompatibility complex class II-encoded HLA-DRB1-DQA1-DQB1 haplotypes is well known. Recent evidence from other autoimmune diseases has suggested that class I-encoded HLA-A and HLA-B gene variants confer HLA-DRB1-DQA1-DQB1-independent effects on disease. Objective: We aimed to explore AAD predisposing effects of HLA-A and -B and further investigate the role of MICA and HLA-DRB1-DQA1-DQB1 in a much larger material than has previously been studied. Design: HLA-A, -B, -DRB1, and -DQB1 and a microsatellite in MICA were genotyped in 414 AAD patients and 684 controls of Norwegian origin. Results: The strongest association was observed for the DRB1 locus, in which the DRB1*03:01 and DRB1*04:04 conferred increased risk of AAD, particularly in a heterozygous combination [odds ratio 22.13; 95% confidence interval (11.39-43.98); P = 6 × 10(-20)]. After conditioning on DRB1, association with AAD was still present for HLA-B and MICA, suggesting the presence of additional risk factors. Conclusions: The major histocompatibility complex harbors multiple risk loci for AAD, in which DRB1 appears to represent the main risk factor.},
  author       = {Skinningsrud, Beate and Lie, Benedicte A and Lavant, Ewa and Carlson, Joyce and Erlich, Henry and Akselsen, Hanne E and Gervin, Kristina and Wolff, Anette B and Erichsen, Martina M and Lövås, Kristian and Husebye, Eystein S and Undlien, Dag E},
  issn         = {1945-7197},
  language     = {eng},
  pages        = {1703--1708},
  publisher    = {ARRAY(0x83fe3c0)},
  series       = {The Journal of clinical endocrinology and metabolism},
  title        = {Multiple Loci in the HLA Complex Are Associated with Addison's Disease.},
  url          = {http://dx.doi.org/10.1210/jc.2011-0645},
  volume       = {96},
  year         = {2011},
}