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.
Statistics from Altmetric.com
Review history and Supplementary material
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.