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SAT0018 Identification of new epistatic interactions with the HLA region in the genetic etiology of psoriasis and psoriatic arthritis
  1. S. Marsal1,
  2. J.M. Hernanz2,
  3. J.D. Cañete3,
  4. E. Fonseca4,
  5. C. Ferrandiz5,
  6. P. Unamuno6,
  7. L. Puig7,
  8. J.L. Fernández-Sueiro4,
  9. R. Sanmartí3,
  10. J. Rodriguez8,
  11. J. Gratacόs9,
  12. E. Dauden10,
  13. J.L. Sánchez-Carazo11,
  14. J.L. Lόpez-Estebaranz12,
  15. D. Moreno-Ramirez13,
  16. R. Queirό14,
  17. C. Montilla15,
  18. J.C. Torre-Alonso16,
  19. J.J. Pérez-Venegas17,
  20. F. Vanaclocha18,
  21. E. Herrera19,
  22. S. Muñoz-Fernández20,
  23. C. González2,
  24. D. Roig21,
  25. A. Erra22,
  26. I. Acosta1,
  27. A. Fernández-Nebro23,
  28. P. Zarco12,
  29. A. Alonso1,
  30. M. Lόpez-Lasanta1,
  31. A. Julià1,
  32. R. Tortosa1
  1. 1Rheumatology Research Group, Vall Hebron Hospital Research Institute, Barcelona
  2. 2Hospital Universitario Gregorio Marañόn, Madrid
  3. 3Hospital Clínic de Barcelona, Barcelona
  4. 4Complejo Hospitalario Juan Canalejo, A Coruña
  5. 5Hospital Universitari Germans Trias i Pujol, Badalona, Barcelona
  6. 6Hospital Universitario de Salamanca, Salamanca
  7. 7Hospital de la Santa Creu i Sant Pau
  8. 8Hospital Universitari de Bellvitge, Barcelona
  9. 9Hospital Parc Taulí, Sabadell, Barcelona
  10. 10Hospital Universitario La Princesa, Madrid
  11. 11Hospital General Universitario de Valencia, Valencia
  12. 12Hospital Universitario Fundaciόn Alcorcόn, Madrid
  13. 13Hospital Universitario Virgen Macarena, Sevilla
  14. 14Hospital Universitario Central de Asturias, Oviedo
  15. 15Hospital Virgen de la Vega, Salamanca
  16. 16Hospital Monte Naranco, Oviedo
  17. 17Hospital de Jerez de la Frontera, Cádiz
  18. 18Hospital Universitario 12 de Octubre, Madrid
  19. 19Hospital Universitario Virgen de la Victoria, Málaga
  20. 20Hospital Universitario Infanta Sofía, Madrid
  21. 21Centre d’Atenciό Especialitzada de Cornellà
  22. 22Hospital Sant Rafael, Barcelona
  23. 23Hospital Regional Universitario Carlos Haya, Málaga, Spain

Abstract

Background Psoriatic Arthritis (PsA) is a complex disease and is present in ∼11% in patients with Psoriasis (Ps). Recently, Genomewide Association Studies (GWAS) have expanded the number of risk loci for Ps in >20 new loci. Two of these genes, ERAP-1 and HLA-C, have been shown to interact epistatically in the risk to develop Ps.

Objectives We have studied the presence of new genetic interactions between Ps risk lci with the HLA region in Purely cutaneous Psoriasis (PsC) and PsA.

Methods Within each Ps risk locus (n=31), the SNP having the highest statistical evidence was selected. The 31 SNPs were genotyped using Taqman technology in a cohort of n=955 PsA, 1,050 PsC and 1,497 hypernormal controls of the Spanish population. The presence of statistically significant gene-gene interactions was performed using a logistic regression model with three parameters to determine the presence of interaction at the allelic level.

Results We replicated the previously described interaction of HLA-C and ERAP1 in the PsC cohort but not in the PsA cohort. We identified, for the first time, a significative epistatic association between HLA-C and SERPINB8. Microarray gene expression studies on cutaneous biopsies corroborate the presence of this interaction at a functional level. In PsA, no statistically significant interactions where identified with variation at HLA-C. However, 6 of the studied genes showed a significant (P<0.05) association with HLA-B27 positivity.

Conclusions The present study has identified new genetic interactions associated with the risk to develop PsC and PsA. The functional study of these interactions will improve our knowledge of the biological basis of these complex diseases.

Disclosure of Interest None Declared

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