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
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
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DOI：
10.2337/diabetes.53.11.3020
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发表时间：
2004-11-01
期刊：
影响因子：
7.7
通讯作者：
Todd, JA
中科院分区：
文献类型：
--
作者：
Smyth, D;Cooper, JD;Todd, JA
在1型糖尿病等常见多因素疾病的遗传分析中，迄今为止，真正的阳性无可辩驳的连锁和关联结果很少。最近，有报道称，编码淋巴蛋白酪氨酸磷酸酶（LYP）中Arg 620 Trp的基因PTPN 22中的单核苷酸多态性（SNP）1858 C>T与1型糖尿病的风险增加相关，该基因已被证明是T细胞活化的负调节剂。在此，我们在1,388个1型糖尿病家族和1,599个病例及1,718个对照组中重复了这些发现，证实了PTPN 22位点与1型糖尿病的关联（基于家族的相对危险度（RR）1.67 [95%CI 1.46-1.91]，病例对照比值比（OR）1.78 [95%CI 1.54-2.06];总体P = 6.02 x 10（-27））。我们还报告了Trp（620）与另一种自身免疫性疾病Graves病相关的证据，在1，734例病例和对照受试者中（P = 6.24 x 10（-4）; OR 1.43 [95%CI 1.17-1.76]）。总之，这些结果表明PTPN 22基因座与自身免疫性疾病有更广泛的关联。
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 antoimmune disease.