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
Author:
Smyth Deborah1, Cooper Jason D.1, Collins Joanne E.2, Heward Joanne M.2, Franklyn Jayne A.2, Howson Joanna M.M.1, Vella Adrian1, Nutland Sarah1, Rance Helen E.1, Maier Lisa1, Barratt Bryan J.3, Guja Cristian4, Ionescu-Tı̂rgovişte Constantin4, Savage David A.5, Dunger David B.6, Widmer Barry6, Strachan David P.7, Ring Susan M.8, Walker Neil1, Clayton David G.1, Twells Rebecca C.J.1, Gough Stephen C.L.2, Todd John A.1
Affiliation:
1. Juvenile Diabetes Research Foundation (JDRF)/Wellcome Trust (WT) Diabetes and Inflammation Laboratory, Cambridge Institute for Medical Research (CIMR), University of Cambridge, Cambridge, U.K 2. Division of Medical Sciences, University of Birmingham, Birmingham, U.K 3. AstraZeneca, Macclesfield, U.K 4. Clinic of Diabetes, Institute of Diabetes, Nutrition and Metabolic Diseases “N. Paulescu,” Bucharest, Romania 5. Department of Medical Genetics, Queen’s University Belfast, Belfast City Hospital, Belfast, Northern Ireland 6. Department of Paediatrics, Addenbrooke’s Hospital, University of Cambridge, Cambridge, U.K 7. Department of Public Health Sciences, St. George’s Hospital Medical School, London, U.K 8. Avon Longitudinal Study of Parents and Children (ALSPAC), University of Bristol, Bristol, U.K
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.
Publisher
American Diabetes Association
Subject
Endocrinology, Diabetes and Metabolism,Internal Medicine
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