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Åke Lernmark

Principal investigator

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

Author

  • M. Maziarz
  • M. Janer
  • J. C. Roach
  • W. Hagopian
  • J. P. Palmer
  • K. Deutsch
  • C. B. Sanjeevi
  • I. Kockum
  • N. Breslow
  • Åke Lernmark

Summary, in English

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

Department/s

  • Diabetes and Celiac Unit
  • EXODIAB: Excellence in Diabetes Research in Sweden

Publishing year

2010

Language

English

Pages

406-415

Publication/Series

Genes and Immunity

Volume

11

Issue

5

Document type

Journal article

Publisher

Nature Publishing Group

Topic

  • Endocrinology and Diabetes

Keywords

  • cell autoantibodies
  • islet
  • insulin autoantibodies
  • autoimmune disease
  • IA-2 autoantibodies
  • islet cell antigen
  • ICA

Status

Published

Research group

  • Diabetes and Celiac Unit

ISBN/ISSN/Other

  • ISSN: 1476-5470