The codon 620 tryptophan allele of the lymphoid tyrosine phosphatase (LYP) gene is a major determinant of Graves' disease
The codon 620 tryptophan allele of the lymphoid tyrosine phosphatase (LYP) gene is a major determinant of Graves' disease
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DOI：
10.1210/jc.2004-1108
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发表时间：
2004-11-01
影响因子：
5.8
通讯作者：
Pearce, SHS
中科院分区：
文献类型：
--
作者：
Velaga, MR;Wilson, V;Pearce, SHS
淋巴酪氨酸磷酸酶 (LYP) 由蛋白酪氨酸磷酸酶 22 (PTPN22) 基因编码，是 T 细胞激活的强大抑制剂。最近，编码 LYP 密码子 620 处功能性精氨酸至色氨酸残基变化的单核苷酸多态性 (SNP) 已被证明与 1 型糖尿病和其他自身免疫性疾病相关。我们使用 PCR 限制性片段 (XcmI) 测定法检查了 549 名患有格雷夫斯病的无关先证者、104 名患有自身免疫性阿狄森氏病的无关受试者和 429 名对照者的密码子 620 多态性的基因型。编码色氨酸 620 残基的 SNP 处的 T 核苷酸存在于 1098 个格雷夫斯病等位基因中的 151 个 (13.8%) 中，而 858 个对照等位基因中的 67 个 (7.8%) 中存在这种情况（chi(2)=17.2，p=3.4x10(-5)；比值比=1.99，5-95% 置信区间 [CI] 1.39 至 2.55）。类似地，密码子 620 SNP 处的 T 核苷酸存在于 208 个阿狄森氏病等位基因中的 26 个中 (12.5%)，而对照组为 7.8%（chi(2)=4.63，p=0.031；比值比=1.69，5-95% CI 1.04 至 2.73）。这些数据表明，这种 LYP 多态性是格雷夫斯病的易感等位基因，具有重大影响，并且可能在许多其他自身免疫性疾病中发挥作用。
The lymphoid tyrosine phosphatase (LYP), encoded by the protein tyrosine phosphatase-22 (PTPN22) gene, is a powerful inhibitor of T cell activation. Recently, a single nucleotide polymorphism (SNP), encoding a functional arginine to tryptophan residue change at LYP codon 620 has been shown to be associated with type 1 diabetes and other autoimmune disorders. We have used a PCR-restriction fragment (XcmI) assay to examine genotypes at the codon 620 polymorphism in 549 unrelated probands with Graves' disease, 104 unrelated subjects with autoimmune Addison's disease and 429 controls. The T nucleotide at the SNP, encoding the tryptophan 620 residue, was present in 151 of 1098 (13.8%) Graves' disease alleles compared to 67 of 858 (7.8%) control alleles (chi(2)=17.2, p=3.4x10(-5); odds ration=1.99, 5-95% confidence intervals [CI] 1.39 to 2.55). Similarly, the T nucleotide at the codon 620 SNP was present in 26 of 208 (12.5%) Addison's disease alleles vs 7.8% of controls (chi(2)=4.63, p=0.031; odds ratio=1.69, 5-95% CI 1.04 to 2.73). These data suggest that this LYP polymorphism is a susceptibility allele for Graves' disease with a major effect, and which is likely to have a role in many other autoimmune conditions.