Associations Between PADI4 Gene Polymorphisms and Rheumatoid Arthritis: An Updated Meta-analysis

Background and Aims Studies investigating the association between the peptidylarginine deiminase 4 (PADI4) gene polymorphisms and rheumatoid arthritis (RA) reported conflicting results. The aim of this meta-analysis was to assess the association between PADI4 gene polymorphisms and RA. Methods A systematic literature search was conducted to identify relevant studies. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were used to estimate the strength of the association. Results A total of 34 studies from 28 articles involving 19859 patients with RA and 25771 healthy controls were included. Significant association of PADI4–94G/A polymorphism and RA was observed (OR = 0.891, 95% CI = 0.833–0.954, p  = 0.001) in the overall study population and in the Asian populations (OR = 0.824, 95% CI = 0.759–0.894, p  = 0.000) respectively. For the –92C/G polymorphism, a significant association was observed (OR = 1.481, 95% CI = 1.166–1.882, p  = 0.001) in Africans. For the –90C/T polymorphism, a significant association was observed (OR = 0.576, 95% CI = 0.381–0.872, p  = 0.009) in the Latin American population. The pooled estimates for the other polymorphisms were not statistically significantly associated with RA (PADI4–104C/T, –89A/G, –96T/C). Conclusions This meta-analysis demonstrates that PADI4–94G/A polymorphism is associated with susceptibility to RA in the overall population and in the Asian population. The PADI4 –92C/G polymorphism confers susceptibility to RA in Africans and the PADI4–90C/T polymorphism was associated with RA in the Latin American population.