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.