The association between the PTPN22 1858C > T variant and type 1 diabetes depends on HLA risk and GAD65 autoantibodies
Maziarz, M. LU ; 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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1654958
- author
- Maziarz, M.
LU
; Janer, M.
; Roach, J. C.
; Hagopian, W.
; Palmer, J. P.
; Deutsch, K.
; Sanjeevi, C. B.
; Kockum, I.
; Breslow, N.
and Lernmark, Åke
LU
- organization
- publishing date
- 2010
- 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
- pmid:20445565
- 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
- 2016-04-01 09:49:14
- date last changed
- 2022-01-25 17:01:20
@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}},
keywords = {{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}},
doi = {{10.1038/gene.2010.12}},
volume = {{11}},
year = {{2010}},
}