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THU0010 Genome-Wide Association Study of Anti-Cyclic Citrullinated Protein-Positive Rheumatoid Arthritis Identifies a New Risk Locus in SLC8A3
  1. A. Julià1,
  2. A. Fernandez-Nebro2,
  3. F. Blanco3,
  4. I. González4,
  5. J.D. Cañete5,
  6. J. Maymό6,
  7. M. Alperi-Lόpez7,
  8. B. Fernández-Gutierrez8,
  9. A. Olivè9,
  10. H. Corominas10,
  11. J. Tornero11,
  12. A. Erra12,
  13. A. González13,
  14. V. Martínez Taboada14,
  15. S. Sánchez15,
  16. I. Acosta Colmán16,
  17. A. Alonso16,
  18. M. Lόpez-Lasanta16,
  19. R. Tortosa16,
  20. S. Marsal16
  1. 1Grup de Recerca de Reumatologia, Vall Hebron Research Institute, Barcelona
  2. 2Hospital Regional Universitario Carlos Haya, Málaga
  3. 3Hospital Juan Canalejo, A Coruña
  4. 4Hospital Universitario La Princesa, Madrid
  5. 5Hospital Clínic de Barcelona
  6. 6Hospital del Mar, Barcelona
  7. 7Hospital Universitario Central de Asturias, Asturias
  8. 8Hospital Clínico San Carlos, Madrid
  9. 9Hospital Universitari Germans Trias i Pujol, Badalona
  10. 10Hospital Moisès Broggi, Sant Joan Despí
  11. 11Hospital Universitario Guadalajara, Guadalajara
  12. 12Hospital Sant Rafael, Barcelona
  13. 13Hospital General de Santiago, Santiago de Compostela
  14. 14Hospital Universitario Marqués de Valdecilla, Santander
  15. 15Hospital General La Mancha Centro, Ciudad Real
  16. 16H. Vall d'Hebron, Barcelona, Spain


Background There is strong evidence that Rheumatoid Arthritis (RA) patients expressing anti-cyclic citrullinated peptide antibodies (ACPA) have a differential genetic background compared to ACPA-negative RA patients.

Objectives We performed a genome-wide association study (GWAS) on ACPA-positive RA patients to identify additional disease susceptibility genes.

Methods A total of 924 ACPA-positive RA patients and 1,524 healthy controls were genotyped in 582,591 single-nucleotide polymorphisms (SNPs) in the discovery phase. The most significant SNPs were then analyzed in an independent cohort of 863 ACPA-positive patients and 1,152 healthy controls.

Results In the discovery phase we found suggestive association (P <5e-4) for 60 novel loci with the risk to develop ACPA-positive RA. In the validation phase, we nominally replicated the association of 12 candidate loci (P<0.05 same direction of effect as in GWAS). Combining the data from the discovery and validation cohorts we found a genome-wide significant association between an intronic SNP in Solute Carrier family 8 gene (SLC8A3) and the risk to develop ACPA-positive RA (OR (95%CI): 1.42 (1.25-1.6), combined P=3.19e-8).

Conclusions This study identified a new locus associated with ACPA-positive RA. These results support the evidence that RA patients positive for ACPA have a specific genetic background.

Disclosure of Interest None declared

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