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THU0462 Anti-Citrullinated Peptide/Protein Antibody (ACPA)-Negative RA Shares Large Proportion of Susceptibility Genes with Acpa-Positive RA
  1. C. Terao1,
  2. K. Ohmura2,
  3. K. Ikari3,
  4. Y. Kochi4,
  5. Y. Okada4,
  6. M. Shimizu1,
  7. T. Kawaguchi1,
  8. M. Takahashi1,
  9. K. Myouzen4,
  10. A. Suzuki4,
  11. M. Kubo4,
  12. R. Yamada1,
  13. A. Taniguchi3,
  14. H. Yamanaka3,
  15. S. Momohara3,
  16. K. Yamamoto4,
  17. F. Matsuda1,
  18. T. Mimori2
  1. 1Center for Genomic Medicine
  2. 2Rheumatology and Clinical Immunology, Kyoto University, Kyoto
  3. 3Institute of Rheumatology, Tokyo Women's Medical University
  4. 4RIKEN, Tokyo, Japan

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

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