Background: Polymorphisms of the peptidylarginine deiminase type 4 (PADI4) gene confer susceptibility to rheumatoid arthritis (RA) in East Asians. However, studies in European populations have produced conflicting results. This study explored the association of PADI4 genotype with RA in a large UK Caucasian population.
Methods: The PADI4_94 (rs2240340) single nucleotide polymorphism (SNP) was directly genotyped in a cohort of unrelated UK Caucasian RA patients (n=3,732) and population controls (n=3,039). Imputed data from the Wellcome Trust Case Control Consortium (WTCCC) was utilised to investigate the association of PADI4_94 with RA in an independent group of RA cases (n=1,859) and controls (n=10,599). A further 56 SNPs spanning the PADI4 gene were investigated for association with RA using data from the WTCCC study.
Results: PADI4_94 genotype was not associated with RA in either the present cohort or the WTCCC cohort. Combined analysis of all RA cases (n=5,591) and controls (n=13,638) gave an overall OR of 1.01 (0.96-1.05, p=0.72). No association with anti-CCP antibodies and no interaction with either shared epitope or PTPN22 was detected. No evidence for association with RA was identified for any of the PADI4 SNPs investigated. Meta-analysis of previously published studies and our data confirmed no significant association between PADI4_94 genotype and RA in people of European descent (OR 1.06, 0.99-1.13, p=0.12).
Conclusion: In the largest study performed to date, we found that, in contrast to Asian populations, PADI4 genotype is not a significant risk factor for RA in people of European ancestry.