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

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.