title: 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.
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.
authors.affiliation: Juvenile Diabetes Research Foundation (JDRF)/Wellcome Trust (WT) Diabetes and Inflammation Laboratory, Cambridge Institute for Medical Research (CIMR), University of Cambridge, Cambridge, UK.
authors.forename: Deborah
authors.initials: D
authors.lastname: Smyth
authors.forename: Jason D
authors.initials: JD
authors.lastname: Cooper
authors.forename: Joanne E
authors.initials: JE
authors.lastname: Collins
authors.forename: Joanne M
authors.initials: JM
authors.lastname: Heward
authors.forename: Jayne A
authors.initials: JA
authors.lastname: Franklyn
authors.forename: Joanna M M
authors.initials: JM
authors.lastname: Howson
authors.forename: Adrian
authors.initials: A
authors.lastname: Vella
authors.forename: Sarah
authors.initials: S
authors.lastname: Nutland
authors.forename: Helen E
authors.initials: HE
authors.lastname: Rance
authors.forename: Lisa
authors.initials: L
authors.lastname: Maier
authors.forename: Bryan J
authors.initials: BJ
authors.lastname: Barratt
authors.forename: Cristian
authors.initials: C
authors.lastname: Guja
authors.forename: Constantin
authors.initials: C
authors.lastname: Ionescu-Tîrgoviste
authors.forename: David A
authors.initials: DA
authors.lastname: Savage
authors.forename: David B
authors.initials: DB
authors.lastname: Dunger
authors.forename: Barry
authors.initials: B
authors.lastname: Widmer
authors.forename: David P
authors.initials: DP
authors.lastname: Strachan
authors.forename: Susan M
authors.initials: SM
authors.lastname: Ring
authors.forename: Neil
authors.initials: N
authors.lastname: Walker
authors.forename: David G
authors.initials: DG
authors.lastname: Clayton
authors.forename: Rebecca C J
authors.initials: RC
authors.lastname: Twells
authors.forename: Stephen C L
authors.initials: SC
authors.lastname: Gough
authors.forename: John A
authors.initials: JA
authors.lastname: Todd
mesh_terms: D000328:Adult; D015551:Autoimmunity / Q000235:genetics*; D002648:Child; D002874:Chromosome Mapping; D003922:Diabetes Mellitus, Type 1 / Q000201:enzymology / Q000235:genetics* / Q000276:immunology; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D009679:Nuclear Family; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases / Q000235:genetics*; D012016:Reference Values; D012044:Regression Analysis
chemical_list: D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases