title: Effects of genetic polymorphisms of programmed cell death 1 and its ligands on the development of ankylosing spondylitis.
abstract: OBJECTIVE
  There is a known association of imbalanced peripheral tolerance and autoimmune diseases. The binding of programmed cell death 1 (PD-1) with its ligands 1 and 2 (PD-L1 and PD-L2) inhibits T-cell proliferation through a negative signal via recruitment of src homology 2-domain-containing tyrosine phosphatase 2. Therefore we evaluated the effect of the PD-1, PD-L1 and PD-L2 genotypes on the occurrence of AS in a population of Taiwanese patients.
  
  
  METHODS
  Genetic polymorphisms of PD-1 G-536A, PD-L1 A8923C and PD-L2 C47103T were identified by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) for 330 AS patients and 330 healthy controls who were matched by age and gender.
  
  
  RESULTS
  Subjects with the PD-1 GG genotype [matched relative risk (RR(m)) 1.78; 95% CI 1.13, 2.81] and the GA genotype (RR(m) 1.59; 95% CI 1.09, 2.31) had significantly greater risk for AS than those with the AA genotype. Subjects with the PD-L2 CT genotype had lower risk for AS than those with the CC genotype (RR(m) 0.01; 95% CI 0.001, 0.06). Interestingly, the combined genotypes of PD-1 G-536A, PD-L1 A8923C and PD-L2 C47103T also appear to be associated with AS development.
  
  
  CONCLUSIONS
  Our results suggest that PD-1 G-536A, PD-L1 A8923C and PD-L2 C47103T polymorphisms are associated with the presence of AS.
authors.affiliation: 1Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.
authors.forename: Chun-Huang
authors.initials: CH
authors.lastname: Huang
authors.forename: Ruey-Hong
authors.initials: RH
authors.lastname: Wong
authors.forename: James Cheng-Chung
authors.initials: JC
authors.lastname: Wei
authors.forename: Ming-Dow
authors.initials: MD
authors.lastname: Tsay
authors.forename: Wei-Chiao
authors.initials: WC
authors.lastname: Chen
authors.forename: Hung-Yin
authors.initials: HY
authors.lastname: Chen
authors.forename: Wei-Ting
authors.initials: WT
authors.lastname: Shih
authors.forename: Sz-Ping
authors.initials: SP
authors.lastname: Chiou
authors.forename: Yi-Chung
authors.initials: YC
authors.lastname: Tu
authors.forename: Hong-Shen
authors.initials: HS
authors.lastname: Lee
mesh_terms: D000328:Adult; D015703:Antigens, CD / Q000235:genetics*; D018122:B7-1 Antigen / Q000235:genetics*; D060890:B7-H1 Antigen; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D061027:Programmed Cell Death 1 Ligand 2 Protein; D012307:Risk Factors; D013167:Spondylitis, Ankylosing / Q000175:diagnosis / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D015703:Antigens, CD; D018122:B7-1 Antigen; D060890:B7-H1 Antigen; C423236:CD274 protein, human; D009363:Neoplasm Proteins; C414207:PCD1 protein, human; C556977:PDCD1LG2 protein, human; D061027:Programmed Cell Death 1 Ligand 2 Protein; D014157:Transcription Factors