Effects of genetic polymorphisms of programmed cell death 1 and its ligands on the development of ankylosing spondylitis

• Published in: Rheumatology (Oxford, England) England), 2011-10, Vol.50 (10), p.1809-1813
• Main Authors: Huang, Chun-Huang, Wong, Ruey-Hong, Wei, James Cheng-Chung, Tsay, Ming-Dow, Chen, Wei-Chiao, Chen, Hung-Yin, Shih, Wei-Ting, Chiou, Sz-Ping, Tu, Yi-Chung, Lee, Hong-Shen
• Format: Article
• Language: English
• Subjects: Adult; Ankylosing spondylitis; Antigens, CD - genetics; Apoptosis; Autoimmune diseases; B7-1 Antigen - genetics; B7-H1 Antigen; Biological and medical sciences; Diseases of the osteoarticular system; Diseases of the spine; Female; Gene polymorphism; Genetic Predisposition to Disease; Genotype; Homology; Humans; Immunological tolerance; Inflammatory joint diseases; Lymphocytes T; Male; Medical sciences; Middle Aged; Neoplasm Proteins - genetics; PD-1 protein; PD-L1 protein; Polymerase Chain Reaction; Polymorphism, Restriction Fragment Length; Polymorphism, Single Nucleotide; Programmed Cell Death 1 Ligand 2 Protein; Protein-tyrosine-phosphatase; Restriction fragment length polymorphism; Risk assessment; Risk Factors; Spondylitis, Ankylosing - diagnosis; Spondylitis, Ankylosing - genetics; Src protein; Transcription Factors - genetics
• ISSN: 1462-0324; 1462-0332
• DOI: 10.1093/rheumatology/ker211

Objectives. 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 (RRm) 1.78; 95% CI 1.13, 2.81] and the GA genotype (RRm 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 (RRm 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.