Genetic Association of PTPN22 Polymorphisms with Autoimmune Hepatitis and Primary Biliary Cholangitis in Japan.
Genetic Association of PTPN22 Polymorphisms with Autoimmune Hepatitis and Primary Biliary Cholangitis in Japan.
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DOI：
10.1038/srep29770
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发表时间：
2016-07-11
影响因子：
4.6
通讯作者：
Ota M
中科院分区：
文献类型：
--
作者：
Umemura T;Joshita S;Yamazaki T;Komatsu M;Katsuyama Y;Yoshizawa K;Tanaka E;Ota M
自身免疫性肝炎(AIH)和原发性胆管炎(PBC)是肝脏特有的自身免疫性疾病，以慢性肝损伤为特征，常导致肝硬变和肝功能衰竭。具体地说，蛋白酪氨酸磷酸酶N22(PTPN22)基因编码淋巴蛋白酪氨酸磷酸酶，它作为T细胞受体信号的负调节因子。PTPN22的错义单核苷酸多态(SNP)(Rs2476601)与许多高加索人的自身免疫性疾病有关。本研究采用TaqMan方法对166例AIH患者、262例PBC患者和322例健康对照的PTPN22基因的9个SNPs进行分析。虽然rs3996649和rs2476601在所有受试者中均为非多态，但rs1217412、rs1217388、rs1217407和rs2488458等位基因频率在AIH组明显低于对照组(均为Pc <； 0.05)。PBC患者PTPN22SNPs与PTPN22SNPs无显著相关性。有趣的是，AAGTCCC单倍型与AIH(OR[OR] = 0.58，P = 0.0067)和PBC(OR = 0.58，P = 0.0048)的抗性显著相关。因此，PTPN22基因中的SNPs可能在日本人对自身免疫性肝病的遗传抵抗中发挥关键作用。
Autoimmune hepatitis (AIH) and primary biliary cholangitis (PBC) are liver-specific autoimmune conditions that are characterized by chronic hepatic damage and often lead to cirrhosis and hepatic failure. Specifically, the protein tyrosine phosphatase N22 (PTPN22) gene encodes the lymphoid protein tyrosine phosphatase, which acts as a negative regulator of T-cell receptor signaling. A missense single nucleotide polymorphism (SNP) (rs2476601) in PTPN22 has been linked to numerous autoimmune diseases in Caucasians. In the present series, nine SNPs in the PTPN22 gene were analyzed in 166 patients with AIH, 262 patients with PBC, and 322 healthy controls in the Japanese population using TaqMan assays. Although the functional rs3996649 and rs2476601 were non-polymorphic in all subject groups, the frequencies of the minor alleles at rs1217412, rs1217388, rs1217407, and rs2488458 were significantly decreased in AIH patients as compared with controls (all Pc < 0.05). There were no significant relationships with PTPN22 SNPs in PBC patients. Interestingly, the AAGTCCC haplotype was significantly associated with resistance to both AIH (odds ratio [OR] = 0.58, P = 0.0067) and PBC (OR = 0.58, P = 0.0048). SNPs in the PTPN22 gene may therefore play key roles in the genetic resistance to autoimmune liver disease in the Japanese.