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-Tîrgovişte, 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

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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 × 10-27). We also report evidence for an association of Trp620 with another autoimmune disorder, Graves' disease, in 1,734 case and control subjects (P = 6.24 × 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 (US)
Pages (from-to)3020-3023
Number of pages4
JournalDiabetes
Volume53
Issue number11
DOIs
StatePublished - Nov 2004

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ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Smyth, D., Cooper, J. D., Collins, J. E., Heward, J. M., Franklyn, J. A., Howson, J. M. M., Vella, A., Nutland, S., Rance, H. E., Maier, L., Barratt, B. J., Guja, C., Ionescu-Tîrgovişte, C., Savage, D. A., Dunger, D. B., Widmer, B., Strachan, D. P., Ring, S. M., Walker, N., ... Todd, J. A. (2004). 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. Diabetes, 53(11), 3020-3023. https://doi.org/10.2337/diabetes.53.11.3020