Slide Session : OS-RHEU-02 ; Rheumatology : Association of Single Nucleotide Polymorphisms of PADI4 Gene with Susceptibility to Rheumatoid Arthritis- Related Lung Disease

Background: Rheumatoid arthritis (RA) causes a myriad of pulmonary complications, including bronchiolitis, bronchiectasis, pleuritis, and interstitial lung disease (ILD). Recently, several studies have shown the association of RA-related lung disease (RA-LD) with the high titers of rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA) which are the most specifi c serologic marker for RA. Single nucleotide polymorphisms (SNPs) in a citrullinating enzyme, peptidyl arginine deiminase type IV (PADI4) have been reproducibly associated with RA susceptibility in several populations. The aim of the present study is to investigate if the SNPs in PADI4 gene are associated with RA-LD. Methods: A total of 103 consecutive RA patients, who satisfi ed the 1987 American College of Rheumatology classifi cation criteria, were genotyped for two nonsynonymous (padi4_89 and padi4_92) and one synonymous (padi4_104) SNPs in PADI4. RA-LD was diagnosed using high-resolution computed tomography of the chest. The following data were collected from medical records: Age, sex, disease duration, smoking history, use of disease-modifying anti-rheumatic drugs, RF, and ACPA. We used the independent t-test and the chi-square test. Multivariate logistic regression analysis was performed to assess the relationship between the SNPs in the PADI4 gene and RA-LD. Results: Of the 103 RA patients, 8 (7.8%) had ILD and 33 (32.0%) had small airway disease. High titers of ACPA (=80 U/mL; p=0.022) and RF (=ULN×3; p=0.008) were signifi cantly associated with susceptibility to RA-LD (Table 1). SNPs and genotypes in exon-3 (padi4_92) of PADI4 showed signifi cant association with susceptibility to RALD (p=0.013, p=0.004, respectively) (Table 2)(Table 3). Conclusions: Our results suggest that SNPs and genotypes in exon-3 (padi4_92) of PADI4 are associated with susceptibility to RA-LD. Further studies are warranted to clarify the mechanisms by which SNPs in the PADI4 gene affect the development of RA-LD.