The programmed cell death 1 gene polymorphisms (PD 1.3 G/A, PD 1.5 C/T and PD 1.9 C/T) and susceptibility to ankylosing spondylitis: a meta-analysis

The objective is to integrate all the eligible studies and investigate whether the programmed cell death 1 (PDCD-1) gene polymorphisms (PD 1.3 G/A, PD 1.5 C/T, and PD 1.9 C/T polymorphism) are correlated with ankylosing spondylitis risk (AS). Ankylosing spondylitis is a chronic inflammatory disease, and several genetic and environmental factors play an important role in the development and progression of AS. Significant associations between PDCD-1 gene polymorphisms (PD 1.3 G/A, PD 1.5 C/T or PD 1.9 C/T) and AS risk have been reported; however, some of these results are controversial.

A systematic online search was performed using PubMed, EMBASE, Web of Science, and the Cochrane Library to identify case-control studies investigating the relationship between PD 1.3 G/A, PD 1.5 C/T, and PD 1.9 C/T polymorphisms and the susceptibility of AS. The pooled odds ratio (OR) with 95 % confidence interval (CI; 95 %) was calculated to assess the associations, and subgroup meta-analyses were performed according to the ethnicity of the study populations.

Five studies involving 909 cases and 982 controls met the inclusion criteria after assessment by two reviewers. Overall, there were no significant associations between PD 1.3 G/A and PD 1.5 C/T polymorphisms and AS risk. With regard to PD 1.9 C/T polymorphism, a significant association was found under the allele contrast model (T vs. C: OR 1.74, 95 % CI 1.48-2.06, P < 0.001), heterozygote model (CT vs. CC: OR 2.43, 95 % CI 1.65-3.59, P < 0.001), homozygote model (TT vs. CC: OR 1.87, 95 % CI 1.30-2.71, P = 0.001), and dominant model (CT/TT vs. CC: OR 2.29, 95 % CI 1.65-3.18, P < 0.001). In the subgroup analysis of ethnicity, no significant associations were found between PD 1.3 G/A, PD 1.5 C/T polymorphisms, and AS risk in either Asian or Caucasian populations. However, our study suggested that PD 1.9 C/T polymorphism was significantly associated with AS in Asian populations (T vs. C: OR 1.72, 95 % CI 1.46-2.04, P < 0.001; CT vs. CC: OR 2.44, 95 % CI 1.56-3.82, P < 0.001; TT vs. CC: OR 1.88, 95 % CI 1.30-2.73, P = 0.001; and CT/TT vs. CC: OR 2.29, 95 % CI 1.58-3.32, P < 0.001) but not in Caucasian populations.

The PD 1.9 C/T polymorphism may be involved in susceptibility to AS, particular in Asian populations; however, no significant associations were found between PD 1.3 G/A, PD 1.5 C/T polymorphisms, and AS risk in either Asians or Caucasians.