Replication of an association between the lymphoid tyrosine phosphatase locus (LYP/PTPN22) with type 1 diabetes, and evidence for its role as a general autoimmunity locus

Deborah Smyth, Jason D Cooper, Joanne E Collins, Joanne M Heward, Jayne A Franklyn, Joanna M M Howson, Adrian Vella, Sarah Nutland, Helen E Rance, Lisa Maier, Bryan J Barratt, Cristian Guja, Constantin Ionescu-Tîrgoviste, David A Savage, David B Dunger, Barry Widmer, David P Strachan, Susan M Ring, Neil Walker, David G ClaytonRebecca C J Twells, Stephen C L Gough, John A Todd

Research output: Contribution to journalArticle (Academic Journal)peer-review

397 Citations (Scopus)

Abstract

In the genetic analysis of common, multifactorial diseases, such as type 1 diabetes, true positive irrefutable linkage and association results have been rare to date. Recently, it has been reported that a single nucleotide polymorphism (SNP), 1858C>T, in the gene PTPN22, encoding Arg620Trp in the lymphoid protein tyrosine phosphatase (LYP), which has been shown to be a negative regulator of T-cell activation, is associated with an increased risk of type 1 diabetes. Here, we have replicated these findings in 1,388 type 1 diabetic families and in a collection of 1,599 case and 1,718 control subjects, confirming the association of the PTPN22 locus with type 1 diabetes (family-based relative risk (RR) 1.67 [95% CI 1.46-1.91], and case-control odds ratio (OR) 1.78 [95% CI 1.54-2.06]; overall P = 6.02 x 10(-27)). We also report evidence for an association of Trp(620) with another autoimmune disorder, Graves' disease, in 1,734 case and control subjects (P = 6.24 x 10(-4); OR 1.43 [95% CI 1.17-1.76]). Taken together, these results indicate a more general association of the PTPN22 locus with autoimmune disease.

Original languageEnglish
Pages (from-to)3020-3
Number of pages4
JournalDiabetes
Volume53
Issue number11
Publication statusPublished - Nov 2004

Keywords

  • Adult
  • Autoimmunity
  • Child
  • Chromosome Mapping
  • Diabetes Mellitus, Type 1
  • Female
  • Genotype
  • Humans
  • Male
  • Nuclear Family
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1
  • Protein Tyrosine Phosphatases
  • Reference Values
  • Regression Analysis

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