The associations between PD-1, CTLA-4 gene polymorphisms and susceptibility to ankylosing spondylitis: a meta-analysis and systemic review

Abstract

Previous surveys had evaluated the effects of the PD-1, CTLA-4 gene polymorphisms on susceptibility to ankylosing spondylitis (AS), but the results remained controversial. To briefly examine these consequences, a comprehensive meta-analysis was conducted to estimate the relationships between PD-1 rs11568821, rs2227982, rs2227981, CTLA-4 +49 A/G and -318 C/T polymorphisms and AS risk. The available articles dated to December 2014 were searched in the PUBMED, MEDLINE and EMBASE databases. The data of the genotypes and/or alleles for the PD-1 rs11568821, rs2227982, rs2227981, CTLA-4 +49 A/G and -318 C/T polymorphisms in the AS and control subjects were extracted, and statistical analysis was conducted by STATA 11.2 software. Summary odds ratios (ORs) with their 95 % confidence intervals (95 % CIs) were calculated to determine the strength of associations with fixed-effects or random-effects models. A total of eight published studies were finally involved in this meta-analysis. Meta-analysis of PD-1 rs2227982 polymorphism under the T allele versus C allele (OR 1.744, 95 % CI 1.477-2.059, P < 0.0001), TT+TC versus CC (OR 2.292, 95 % CI 1.654-3.175, P < 0.0001), TT versus CC (OR 1.883, 95 % CI 1.299-2.729, P = 0.001) revealed a significant association with AS. Our meta-analysis demonstrated that the rs2227982 polymorphism in the PD-1 gene might contribute to AS susceptibility. However, further studies with large sample sizes and among different ethnicity populations should be required to confirm this association.

Association of rs10204525 genotype GG and rs2227982 CC combination in programmed cell death 1 with hepatitis B virus infection risk

“…Rs2227982, which was associated with the risk and disease progression of ankylosing spondylitis and breast cancer in previous reports, [21,22] was revealed to be relevant to HBV susceptibility in our study. Rs2227982 locates in the 5th exon of PD-1 and its polymorphism leads to a nonsynonymous mutation and results in an amino acid substitution (Ala to Val) during protein synthesis, which may influence the function of PD-1.…”

Association of the HLA‐B27 antigen and the CTLA4 gene CT60/rs3087243 polymorphism with ankylosing spondylitis in Algerian population: A case–control study

“…It was recently associated with the AS risk in a Chinese study (Wang, Wang, Tan, Wang, & Yuan, ). However, results are controversial, some findings could not reveal any association (Barton et al., ; Pincerati, Dalla‐Costa, & Petzl‐Erler, ) such as a recent meta‐analysis (Chen et al., ). In this case–control study, we investigated the CTLA4 CT60 polymorphism and the HLA‐B27 allele genotyping.…”

Liquid biopsy in targeting gene polymorphism related to the response within immunocheckpoint inhibitors therapeutic regimen

“…GG genotype variant altered tumour necrosis factor-a (TNF-a) to increase levels in HBV patients [38]. PDCD-1.9 (rs2227982) has been evaluated in terms of breast cancer [39], ovarian cancer [40], ankylosing spondylitis [41], multiple myeloma [18] and chronic HBV infection and its oncogenity [19]. This polymorphism increases the probability and severity of the disease in case of ankylosing spondylitis and breast cancer [39,41].…”

“…PDCD-1.9 (rs2227982) has been evaluated in terms of breast cancer [39], ovarian cancer [40], ankylosing spondylitis [41], multiple myeloma [18] and chronic HBV infection and its oncogenity [19]. This polymorphism increases the probability and severity of the disease in case of ankylosing spondylitis and breast cancer [39,41]. Simultaneously, the same reserchers have found that C > T variant reduces the risk of breast cancer [39] and raises the risk of ovarian cancer [40].…”