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淋巴细胞酪氨酸磷酸酶基因座（LYP/PTPN22）与1型糖尿病之间关联的重复研究，及其作为一般自身免疫基因座作用的证据。

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.

作者信息

Smyth Deborah, Cooper Jason D, Collins Joanne E, Heward Joanne M, Franklyn Jayne A, Howson Joanna M M, Vella Adrian, Nutland Sarah, Rance Helen E, Maier Lisa, Barratt Bryan J, Guja Cristian, Ionescu-Tîrgoviste Constantin, Savage David A, Dunger David B, Widmer Barry, Strachan David P, Ring Susan M, Walker Neil, Clayton David G, Twells Rebecca C J, Gough Stephen C L, Todd John A

机构信息

Juvenile Diabetes Research Foundation (JDRF)/Wellcome Trust (WT) Diabetes and Inflammation Laboratory, Cambridge Institute for Medical Research (CIMR), University of Cambridge, Cambridge, UK.

出版信息

Diabetes. 2004 Nov;53(11):3020-3. doi: 10.2337/diabetes.53.11.3020.

DOI:10.2337/diabetes.53.11.3020

PMID:15504986

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.

摘要

在对常见多因素疾病（如1型糖尿病）的基因分析中，迄今为止，真正阳性且无可辩驳的连锁和关联结果一直很少见。最近有报道称，在编码淋巴细胞蛋白酪氨酸磷酸酶（LYP）中第620位精氨酸突变为色氨酸的PTPN22基因中，单核苷酸多态性（SNP）1858C>T与1型糖尿病风险增加相关。该淋巴细胞蛋白酪氨酸磷酸酶已被证明是T细胞活化的负调节因子。在此，我们在1388个1型糖尿病家庭以及1599例病例和1718例对照受试者中重复了这些发现，证实了PTPN22基因座与1型糖尿病的关联（基于家系的相对风险（RR）为1.67 [95%可信区间1.46 - 1.91]，病例对照优势比（OR）为1.78 [95%可信区间1.54 - 2.06]；总体P = 6.02×10⁻²⁷）。我们还报告了在1734例病例和对照受试者中，色氨酸（620）与另一种自身免疫性疾病——格雷夫斯病相关的证据（P = 6.24×10⁻⁴；OR 1.43 [95%可信区间1.17 - 1.76]）。综上所述，这些结果表明PTPN22基因座与自身免疫性疾病存在更普遍的关联。