Response to ‘Peptidyl arginine deiminase type IV (PADI4) haplotypes interact with shared epitope regardless of anti-cyclic citrullinated peptide antibody or erosive joint status in rheumatoid arthritis: a case control study’

Rheumatoid arthritis (RA) is a complex polygenic disease characterized by progressive joint destruction. Anti-citrullinated peptide antibody (ACPA) is the most specific autoantibody for RA. Genetic polymorphisms in the PADI4 gene, encoding citrullinating enzyme peptidylarginine deiminase 4 (PADI4), have been associated with susceptibility to RA [1,2]. They have also been reported to be associated with radiographic joint destruction in patients with RA [3,4]. We focused on ACPA-negative RA patients to investigate whether a PADI4 polymorphism is associated with joint damage in ACPA-negative patients. DNA samples from 122 Japanese ACPA-negative RA patients were used for the study; 81.1% were female, 51.6% were rheumatoid factor (RF)-positive, and the mean age was 55 years. Sharp/van der Heijde score of the hands at a 5-year disease duration, which represents joint damage, was scored and log-transformed as described elsewhere [4]. Single-nucleotide polymorphism (SNP) rs2240340 was selected and genotyped by using a TaqMan method as described elsewhere [4]. The genetic risk of joint damage associated with rs2240340 was assessed by multiple regression analysis adjusted for HLA-DRB1 shared-epitope alleles and RF that are thought to be associated with joint damage in patients with RA [4].