PADI4 Polymorphisms in Iranian Patients with Rheumatoid Arthritis

Aim: Rheumatoid arthritis (RA) is a chronic autoimmune disease which affects many tissues and organs, but majorly attacks synovial joints. Beyond the major histocompatibility complex (MHC) genes, Peptidyl arginine deiminase type IV (PADI4) has been suggested to be associated with RA susceptibility. Evidence regarding the association of PADI4 single nucleotide polymorphisms (SNP) and RA is controversial, thus we conducted this large-scale case-control study to assess the association of rs874881 and rs11203367 PADI4 SNPs with susceptibility to RA. Materials and Methods: Study population (including 665 RA patients and 392 sex-, age-, and ethnicity-matched healthy controls) were enrolled from Rheumatology Research Center of Tehran University of Medical Sciences, Shariati hospital. Results: Allele or genotype frequencies of the investigated PADI4 SNPs were not different between RA patients and healthy subjects; genotypes (expressed as odds ratios) of rs11203367 [TT 0.98 (0.68-1.4), CT 0.93 (0.71-1.24), P value > 0.05] and rs874881 [CC 1.02 (0.71-1.46), CG (0.70-1.39), p value > 0.05] did not affect RA risk. Disease severity score DAS28, RF and anti-CCP antibodies of RA patients were not different between various genotypes of PADI4 SNPs. Conclusions: These findings were similar for haplotypes and diplotypes of rs11203367 and rs874881 PADI4 SNPs. In conclusion, in this case-control study with sufficient sample size to detect associations, we observed that PADI4 SNPS rs11203367 and rs874881 do not significantly determine RA susceptibility; which is in line with studies of some European populations. It seems RA pathogenesis might be different among various ethnicities, which encourage us to consider these differences in developing therapeutic interventions for management of patients.