PTPN22基因多态性与自身免疫性内分泌疾病  

The single nudeotide polymorphism of the protein tyrosine phosphatase-22 gene and autoimmune endocrine diseases

作　　者：郑瑞芝[1] 李蓉[1] 张素华[1] 

机构地区：[1]重庆医科大学附属第一医院内分泌科,400016

出　　处：《国际内分泌代谢杂志》2007年第2期89-91,共3页International Journal of Endocrinology and Metabolism

基　　金：重庆市卫生局科学基金资助项目（04-2-111）

摘　　要：蛋白酪氨酸磷酸酶非受体型22（PTPN22）基因位于染色体1p13．3-13．1，编码淋巴酪氨酸磷酸酶（LYP）。它通过与S忧酪氨酸激酶C端（Csk）相互作用，使已磷酸化的S忧家族Lck、Fyn和Zap-70激酶脱磷酸化，下调T细胞信号。另外，LYP还通过与Csk结合协同抑制T细胞信号，与转接分子——生长因子受体连接蛋白2（Grb2）相互作用，在T细胞信号中起负调节作用。研究发现，FTPN22基因C1858T位点错义突变，引起LYP蛋白620位密码子由精氨酸突变为色氨酸，与Csk亲和力明显降低，导致T细胞活性增强，可能诱发自身免疫性疾病。近来研究表明，该基因突变与1型糖尿病、Graves病和桥本甲状腺炎等多种自身免疫性内分泌疾病相关。Protein tyrosine phosphatase, non-receptor 22 （PIPN22）gene locates in chromosome lp13.3- 13.1, which encodes a lymphoid protein tyrosine phosphatase （LYP）. It may be involved in preventing spontaneous T-cell activation by dephosphorylating and inactivating T-cell receptor-associated C-terminal Src tyrosine kinase （Csk）, down regulating T-cell signal. In addition, LYP inhibits T-cell activation by interacting with Csk. Probably it acts as a downregulator by interacting with the adaptor molecule growth factor receptor-bound protein 2（Grb2）. A missense mutant（C18587T, R620W）may decrease the binding affinity of LYP to CSK and result in higher T-cell activation and induce autoimmune disorders. Recently, a missense mutation in the PIPN22 gene has been shown to be associated with multiple autoimmune endocrine diseases including type 1 diabetes, Graves＇ disease and Hashimoto＇ s thyroiditis.

关 键 词：PTPN22 淋巴酪氨酸磷酸酶 1型糖尿病 GRAVES病 自身免疫性疾病 T淋巴细胞 

分 类 号：R593[医药卫生—内科学]