TY - JOUR
T1 - Replication of an association between the lymphoid tyrosine phosphatase locus with type 1 diabetes, and evidence for its role as a general autoimmunity locus
AU - Smyth, D
AU - Cooper, JD
AU - Collins, Joanne
AU - King, Joanne
AU - Franklyn, Jayne
AU - Howson, JMM
AU - Vella, A
AU - Nutland, S
AU - Rance, HE
AU - Maier, L
AU - Barratt, BJ
AU - Guja, C
AU - Ionescu-Tirgoviste, C
AU - Savage, DA
AU - Dunger, DB
AU - Widmer, B
AU - Strachan, DP
AU - Ring, SM
AU - Walker, N
AU - Clayton, DG
AU - Twells, RCJ
AU - Gough, Stephen
AU - Todd, JA
PY - 2004/1/1
Y1 - 2004/1/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=7044253358&partnerID=8YFLogxK
U2 - 10.2337/diabetes.53.11.3020
DO - 10.2337/diabetes.53.11.3020
M3 - Article
C2 - 15504986
SN - 0012-1797
VL - 53
SP - 3020
EP - 3023
JO - Diabetes
JF - Diabetes
ER -