THU0462 Anti-Citrullinated Peptide/Protein Antibody (ACPA)-Negative RA Shares Large Proportion of Susceptibility Genes with Acpa-Positive RA. (10th June 2014)

• Record Type: Journal Article
• Authors: Terao, C.; Ohmura, K.; Ikari, K.; Kochi, Y.; Okada, Y.; Shimizu, M.; Kawaguchi, T.; Takahashi, M.; Myouzen, K.; Suzuki, A.; Kubo, M.; Yamada, R.; Taniguchi, A.; Yamanaka, H.; Momohara, S.; Yamamoto, K.; Matsuda, F.; Mimori, T.
• Is Part Of: Annals of the rheumatic diseases. Volume 73:Supplement 2(2014)
• Page Start: 343
• Page End: 343
• Publication Date: 2014-06-10
• Subjects: Rheumatism -- Periodicals; 616.723005
• DOI: 10.1136/annrheumdis-2014-eular.3219
• Languages: English
• ISSNs: 0003-4967

Abstract

Abstract : Background: Susceptibility genes for anti-citrullinated peptide/protein antibodies (ACPA)-positive rheumatoid arthritis (RA) have been successfully discovered by the development of genome-wide association studies (GWAS). However, little is known about the genetic background of ACPA-negative RA. Objectives: We intended to clarify genetic background of ACPA-negative RA and compare susceptibility genes between ACPA-negative and -positive RA. Methods: We performed a meta-analysis of GWAS comprising 670 ACPA-negative RA and 16, 891 controls for 1, 948, 138 markers, followed by a replication study of the top 35 SNPs using 916 cases and 3, 764 controls. Inverse-variance method was applied to assess overall effects. To assess overlap of susceptibility genes between ACPA-positive and -negative RA, odds ratios (ORs) of the 21 susceptibility markers to RA in Japanese were compared between the two subsets. In addition, SNPs were stratified by the p-values in GWAS meta-analysis for either ACPA-positive RA or ACPA-negative RA to address the question whether weakly-associated genes were also shared. The correlations between ACPA-positive RA and the subpopulations of ACPA-negative RA (rheumatoid factor (RF)-positive and RF-negative subsets) were also addressed. Results: Rs6904716 in LEMD2 of the HLA locus showed a borderline association with ACPA-negative RA (overall p=5.7x10 –8 ), followed by rs6986423 in CSMD1 (p=2.4x10 –6 ) and rs17727339 in FCRL3 (p=1.4x10 –5 ). ACPA-negative RA showed significant correlations of ORs with ACPA-positive RA for the 21 susceptibility SNPs and non-HLA SNPs with p-values far from significance. These significant correlations with ACPA-positive RA were true for ACPA-negative RF-positive and ACPA-negative RF-negative RA. On the contrary, positive correlations were not observed between the ACPA-negative two subpopulations. Conclusions: Many of the susceptibility genes were shared between ACPA-positive and -negative RA. Acknowledgements: We'd like to thank all doctors who helped us to collect DNA samples from patients with ACPA-negative RA. We'd like to thank especially Drs. Takao Fujii, Hiromu Ito, Motomu Hashimoto and Moritoshi Furu for their effort for sample accumulation. Disclosure of Interest: : None declared DOI: 10.1136/annrheumdis-2014-eular.3219