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The association between the PTPN22 1858C > T variant and type 1 diabetes depends on HLA risk and GAD65 autoantibodies

Maziarz, M.; Janer, M.; Roach, J. C.; Hagopian, W.; Palmer, J. P.; Deutsch, K.; Sanjeevi, C. B.; Kockum, I.; Breslow, N. and Lernmark, Åke LU (2010) In Genes and Immunity 11(5). p.406-415
Abstract
The single nucleotide polymorphism 1858C> T in the PTPN22 gene is associated with type 1 diabetes (T1D) in several populations. Earlier reports have suggested that the association may be modified by human leukocyte antigen (HLA), as well as by islet autoantibodies. In a large case-control study of Swedish incident T1D patients and controls, 0-34 years of age, we tested whether the odds ratio (OR) measure of association was dependent on HLA or autoantibodies against the islet autoantigens glutamic acid decarboxylase 65 kDa autoantibodies (GADA), insulin, islet antigen-2, or islet cell. The association between the carrier status of 1858C> T allele in PTPN22 (PTPN22(CT + TT)) and T1D was modified by HLA. In addition, in GADA-positive... (More)
The single nucleotide polymorphism 1858C> T in the PTPN22 gene is associated with type 1 diabetes (T1D) in several populations. Earlier reports have suggested that the association may be modified by human leukocyte antigen (HLA), as well as by islet autoantibodies. In a large case-control study of Swedish incident T1D patients and controls, 0-34 years of age, we tested whether the odds ratio (OR) measure of association was dependent on HLA or autoantibodies against the islet autoantigens glutamic acid decarboxylase 65 kDa autoantibodies (GADA), insulin, islet antigen-2, or islet cell. The association between the carrier status of 1858C> T allele in PTPN22 (PTPN22(CT + TT)) and T1D was modified by HLA. In addition, in GADA-positive T1D, the OR was 2.83 (2.00, 3.99), whereas in GADA-negative T1D, the OR was 1.41 (0.98, 2.04) (P for comparison = 0.007). The OR of association between PTPN22(CT + TT) and GADA-positive T1D declined with increasing HLA-risk category from 6.12 to 1.54 (P = 0.003); no such change was detected in GADA-negative T1D (P = 0.722) (P for comparison = 0.001). However, the absolute difference in risk between PTPN22(CC) and PTPN22(CT + TT) subjects with high-risk HLA was five times higher than that for subjects with low-risk HLA. We hypothesize that the altered T-cell function because of the PTPN22(1858C> T) polymorphism is exclusively associated with GADA-positive T1D at diagnosis. Genes and Immunity (2010) 11, 406-415; doi: 10.1038/gene.2010.12; published online 6 May 2010 (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
cell autoantibodies, islet, insulin autoantibodies, autoimmune disease, IA-2 autoantibodies, islet cell antigen, ICA
in
Genes and Immunity
volume
11
issue
5
pages
406 - 415
publisher
Nature Publishing Group
external identifiers
  • wos:000280150200005
  • scopus:77954887535
ISSN
1476-5470
DOI
10.1038/gene.2010.12
language
English
LU publication?
yes
id
0f2b0c42-757c-43c1-bc7a-05aad23e2120 (old id 1654958)
date added to LUP
2010-08-30 13:54:13
date last changed
2018-07-08 03:00:28
@article{0f2b0c42-757c-43c1-bc7a-05aad23e2120,
  abstract     = {The single nucleotide polymorphism 1858C> T in the PTPN22 gene is associated with type 1 diabetes (T1D) in several populations. Earlier reports have suggested that the association may be modified by human leukocyte antigen (HLA), as well as by islet autoantibodies. In a large case-control study of Swedish incident T1D patients and controls, 0-34 years of age, we tested whether the odds ratio (OR) measure of association was dependent on HLA or autoantibodies against the islet autoantigens glutamic acid decarboxylase 65 kDa autoantibodies (GADA), insulin, islet antigen-2, or islet cell. The association between the carrier status of 1858C> T allele in PTPN22 (PTPN22(CT + TT)) and T1D was modified by HLA. In addition, in GADA-positive T1D, the OR was 2.83 (2.00, 3.99), whereas in GADA-negative T1D, the OR was 1.41 (0.98, 2.04) (P for comparison = 0.007). The OR of association between PTPN22(CT + TT) and GADA-positive T1D declined with increasing HLA-risk category from 6.12 to 1.54 (P = 0.003); no such change was detected in GADA-negative T1D (P = 0.722) (P for comparison = 0.001). However, the absolute difference in risk between PTPN22(CC) and PTPN22(CT + TT) subjects with high-risk HLA was five times higher than that for subjects with low-risk HLA. We hypothesize that the altered T-cell function because of the PTPN22(1858C> T) polymorphism is exclusively associated with GADA-positive T1D at diagnosis. Genes and Immunity (2010) 11, 406-415; doi: 10.1038/gene.2010.12; published online 6 May 2010},
  author       = {Maziarz, M. and Janer, M. and Roach, J. C. and Hagopian, W. and Palmer, J. P. and Deutsch, K. and Sanjeevi, C. B. and Kockum, I. and Breslow, N. and Lernmark, Åke},
  issn         = {1476-5470},
  keyword      = {cell autoantibodies,islet,insulin autoantibodies,autoimmune disease,IA-2 autoantibodies,islet cell antigen,ICA},
  language     = {eng},
  number       = {5},
  pages        = {406--415},
  publisher    = {Nature Publishing Group},
  series       = {Genes and Immunity},
  title        = {The association between the PTPN22 1858C > T variant and type 1 diabetes depends on HLA risk and GAD65 autoantibodies},
  url          = {http://dx.doi.org/10.1038/gene.2010.12},
  volume       = {11},
  year         = {2010},
}