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OP0021 Genetic Factors for the Severity of ACPA-Negative Rheumatoid Arthritis in Two Cohorts of Early Disease: A Genome-Wide Study
  1. D. De Rooy1,
  2. R. Tsonaka2,
  3. M. Andersson3,
  4. K. Forslind3,
  5. A. Zhernakova4,
  6. C. de Kovel5,
  7. B. Koeleman5,
  8. D. van der Heijde1,
  9. T. Huizinga1,
  10. R. Toes1,
  11. J. Houwing-Duistermaat2,
  12. B. Svensson3,
  13. A. van der Helm-van Mil1
  1. 1Rheumatology
  2. 2Medical Statistics, Lumc, Leiden, Netherlands
  3. 3Rheumatology, Institution of Clinical Science, Lund University, Skåne University Hospital, Lund, Sweden
  4. 4Genetics, umcg, Groningen
  5. 5Medical Genetics, umc, Utrecht, Netherlands


Background ACPA-negative and ACPA-positive Rheumatoid Arthritis (RA) are increasingly regarded as separate clinical entities. Although ACPA-negative patients have a less severe disease course at group level, considerable inter-individual differences in the amount of joint destruction occur.

Objectives As no studies focusing on genetic risk factors underlying the differences in joint destruction in ACPA-negative patients have been performed thus far, we performed the present study.

Methods A Genome-Wide Association Study was performed using Illumina Human CytoSNP-12v2 in relation to radiographic joint destruction in 276 ACPA-negative early RA-patients included in the Leiden Early Arthritis Clinic (EAC). According to the Bonferroni correction on the number of tested SNPs, the threshold for genome wide significance was p<2x10-7. Subsequently, the significant SNPs were evaluated for association with the progression of radiographic joint destruction in 253 ACPA-negative early RA-patients included in the BARFOT-study. As 11 uncorrelated SNPs were tested, the Bonferroni threshold for significance was 0.0045. In all patients, joint destruction was measured by Sharp-van der Heijde Score with good reproducibility.

Results 33 SNPs associated significantly to the severity of joint damage (p<2x10-7) in phase-1. In phase-2, two SNPs showed a trend towards a significant association with joint damage, rs2833522 (p=0.0049) and rs17763915 (p=0.047). A combined analysis of both the Leiden and BARFOT datasets of rs2833522 showed a highly significant association with joint destruction (p=3.57x10-9), the presence of the minor allele associated with more severe damage.

Conclusions Rs2833522 might be associated with the severity of joint damage in ACPA-negative RA. Larger, longitudinal, studies are needed for confirmation.

Acknowledgements This work is supported by the Masterswitch project and BtheCure project. The work of Annette van der Helm-van Mil is supported by the Dutch organization for scientific research (ZonMW). The Dutch Arthritis Foundation (Reumafonds) provided financial support for the genotyping.

Disclosure of Interest None Declared

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