Investigation of polymorphisms in the PADI4 gene in determining severity of inflammatory polyarthritis

Background: A functional haplotype of the peptidylarginine deiminase 4 (PADI4) gene has recently been identified as a rheumatoid arthritis susceptibility gene in a Japanese but not in a UK population. One possible explanation for this disparity is that the gene determines severity of rather than susceptibility to inflammatory polyarthritis (IP) and that the UK and Japanese cohorts differed in terms of outcome. Aim: To examine the association between individual PADI4 single nucleotide polymorphisms ( SNPs) and haplotypes, with the development and severity of erosions by five years in patients with IP. Methods: 438 patients from the NOAR inception cohort of patients with IP were x rayed five years after presentation with early IP. Association with four exonic SNPs ( padi4_89*G/A, padi4_90*T/C, padi4_92*G/C, and padi4_104*T/C), mapping to the PADI4 gene and defining a haplotype previously reported to be associated with rheumatoid arthritis, was investigated. Patients were compared for the presence, extent, and progression of erosions by five years and the presence of antibodies to citrullinated peptide (anti-CCP antibodies). Results: There was no association between individual PADI4 SNPs or haplotypes and the development or extent of erosions by five years. Restricting analysis to patients who satisfied ACR criteria for rheumatoid arthritis by five years did not alter the conclusions. No association with presence of anti-CCP antibodies was detected. Conclusions: No evidence was found for association of the PADI4 gene with severity as assessed by erosive outcome at five years or with presence of anti-CCP antibodies in patients with IP.