title: Associations of the PTPN22 and CTLA-4 genetic polymorphisms with Taiwanese ankylosing spondylitis.
abstract: Ankylosing spondylitis (AS) is an autoimmune disease, and the imbalance of peripheral tolerance is involved in its pathogenesis. Importantly, the negative signal of activated T cells plays a crucial role in the balance of peripheral tolerance. It has been postulated that human protein tyrosine phosphatase nonreceptor 22 (PTPN22) and cytotoxic T-lymphocyte antigen-4 (CTLA-4) genes encode proteins that are actively involved in regulating T-cell activation. Therefore, we evaluated the effects of PTPN22 and CTLA-4 genotypes on the occurrence of AS. Genetic polymorphisms of PTPN22 -1123G/C and CTLA-4 +49A/G were identified by polymerase chain reaction for 391 AS patients and 391 healthy controls. Subjects with PTPN22 CC and GC genotypes had a greater risk of AS occurrence than those with PTPN22 GG genotype [relative risk = 1.39, 95 % confidence interval (95 % CI) 1.03-1.88]. Further, subjects with PTPN22 CC/CTLA-4 AA or PTPN22 GC/CTLA-4 AA genotypes had 1.90-fold (95 % CI 1.02-3.49) greater risk of AS development than those with other combinations of PTPN22 and CTLA-4 genotypes. Our findings indicated that PTPN22 -1123G/C and CTLA-4 +49A/G genetic polymorphisms have a combined effect on the development of AS.
authors.affiliation: Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.
authors.forename: Chun-Huang
authors.initials: CH
authors.lastname: Huang
authors.forename: James Cheng-Chung
authors.initials: JC
authors.lastname: Wei
authors.forename: Chun-Chieh
authors.initials: CC
authors.lastname: Chen
authors.forename: Chih-Shien
authors.initials: CS
authors.lastname: Chuang
authors.forename: Chia-Hsuan
authors.initials: CH
authors.lastname: Chou
authors.forename: Yu-Jie
authors.initials: YJ
authors.lastname: Lin
authors.forename: Ming-Fuu
authors.initials: MF
authors.lastname: Wang
authors.forename: Ruey-Hong
authors.initials: RH
authors.lastname: Wong
mesh_terms: D000328:Adult; D044466:Asian People / Q000235:genetics*; D060908:CTLA-4 Antigen / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D010641:Phenotype; D011110:Polymorphism, Genetic; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22 / Q000235:genetics*; D012307:Risk Factors; D013167:Spondylitis, Ankylosing / Q000208:ethnology / Q000235:genetics* / Q000276:immunology; D013624:Taiwan / Q000453:epidemiology
chemical_list: D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; C516765:PTPN22 protein, human; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22