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.
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.
Smyth
Deborah
D
Juvenile Diabetes Research Foundation (JDRF)/Wellcome Trust (WT) Diabetes and Inflammation Laboratory, Cambridge Institute for Medical Research (CIMR), University of Cambridge, Cambridge, UK.
Cooper
Jason D
JD
Collins
Joanne E
JE
Heward
Joanne M
JM
Franklyn
Jayne A
JA
Howson
Joanna M M
JM
Vella
Adrian
A
Nutland
Sarah
S
Rance
Helen E
HE
Maier
Lisa
L
Barratt
Bryan J
BJ
Guja
Cristian
C
Ionescu-Tîrgoviste
Constantin
C
Savage
David A
DA
Dunger
David B
DB
Widmer
Barry
B
Strachan
David P
DP
Ring
Susan M
SM
Walker
Neil
N
Clayton
David G
DG
Twells
Rebecca C J
RC
Gough
Stephen C L
SC
Todd
John A
JA
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
D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases