title: Genetic Association of PTPN22 Polymorphisms with Autoimmune Hepatitis and Primary Biliary Cholangitis in Japan.
abstract: 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.
authors.affiliation: Department of Medicine, Division of Hepatology and Gastroenterology, Shinshu University School of Medicine, Matsumoto, Japan.
authors.forename: Takeji
authors.initials: T
authors.lastname: Umemura
authors.affiliation: Department of Medicine, Division of Hepatology and Gastroenterology, Shinshu University School of Medicine, Matsumoto, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Joshita
authors.affiliation: Department of Medicine, Division of Hepatology and Gastroenterology, Shinshu University School of Medicine, Matsumoto, Japan.
authors.forename: Tomoo
authors.initials: T
authors.lastname: Yamazaki
authors.affiliation: Department of Medicine, Division of Hepatology and Gastroenterology, Shinshu University School of Medicine, Matsumoto, Japan.
authors.forename: Michiharu
authors.initials: M
authors.lastname: Komatsu
authors.affiliation: Department of Pharmacy, Shinshu University Hospital, Matsumoto, Japan.
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Katsuyama
authors.affiliation: Department of Gastroenterology, NHO Shinshu Ueda Medical Center, Ueda, Japan.
authors.forename: Kaname
authors.initials: K
authors.lastname: Yoshizawa
authors.affiliation: Department of Medicine, Division of Hepatology and Gastroenterology, Shinshu University School of Medicine, Matsumoto, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Tanaka
authors.affiliation: Department of Legal Medicine, Shinshu University School of Medicine, Matsumoto, Japan.
authors.forename: Masao
authors.initials: M
authors.lastname: Ota
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002761:Cholangitis / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D006239:Haplotypes; D019693:Hepatitis, Autoimmune / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics*; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D020641:Polymorphism, Single Nucleotide; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22 / Q000235:genetics*
chemical_list: C516765:PTPN22 protein, human; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22