Abstract

Non-steroidal anti-inflammatory drugs (NSAIDs) are the main triggers of drug hypersensitivity reactions. Such reactions can be pharmacologically or immunologically mediated, but in both cases individual susceptibility can be influenced by genetic factors. Polymorphisms in centrosomal protein of 68 kDa (CEP68) have been associated with pharmacologically mediated NSAIDs reactions. Here, we evaluated this gene in immunologically mediated single-NSAID-induced urticaria/angioedema or anaphylaxis (SNIUAA) by analyzing 52 single nucleotide polymorphisms in CEP68 in 176 patients and 363 NSAIDs-tolerant controls. Two intronic variants (rs2241160 and rs2241161) were significantly associated with an increased risk of SNIUAA, suggesting CEP68 to be a key player in both types of NSAIDs hypersensitivity. However, we found no overlap with genetic variants previously associated with pharmacologically mediated hypersensitivity, pointing to a complex role for this gene and its potential use in the development of biomarkers of clinical utility to diagnose patients at risk of these reactions and to differentiate entities.

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Acknowledgements

This work was supported by grants co-funded by the European Regional Development Fund (ERDF), from the Carlos III National Health Institute (ARADyAL network RD16/0006/0001, RD16/0006/004, RD16/0006/0007, RD16/0006/0019, PI15/00303, and PI17/01593), and the Health Government of Andalusia (PI-0463-2013), and Junta de Extremadura (IB16170). JA Cornejo-García is a researcher from the Miguel Servet Program (Ref CP14/00034), JR Perkins from the Sara Borrell Program (Ref CD14/00242), and I Doña from the Juan Rodés Program (Ref JR15/0036both from the Carlos III National Health Institute, Spanish Ministry of Economy and Competitiveness). M Acosta-Herrera is recipient of a Juan de la Cierva fellowship (FJCI-2015-24028) from the Spanish Ministry of Economy, Industry and Competitiveness. We thank the Malaga Hospital-IBIMA Biobank, belonging to the Andalusian Public Health System Biobank and the National Biobank Platform (project PT13/ 0010/0006, PT13/0010/0033), for sample management, and Dr. Juan Miguel Gómez Zumaquero from the Genomic Unit of IBIMA for his help with genotyping.

Author information

Affiliations

  1. Research Laboratory, IBIMA, Regional University Hospital of Malaga, UMA, Malaga, Spain

    • James R. Perkins
    • , María C. Plaza-Serón
    • , Raquel Jurado-Escobar
    • , Cristobalina Mayorga
    •  & José A. Cornejo-García
  2. ARADyAL Network. Instituto de Salud Carlos III, Madrid, Spain

    • James R. Perkins
    • , Inmaculada Doña
    • , Elena García-Martín
    • , María Isidoro-García
    • , Joan Bartra
    • , Cristobalina Mayorga
    • , María J. Torres
    •  & José A. Cornejo-García
  3. Instituto de Parasitología y Biomedicina López-Neyra, IPBLN-CSIC, P.T.S., Granada, Spain

    • Marialbert Acosta-Herrera
  4. Allergy Unit, IBIMA, Regional University Hospital of Malaga, UMA, Malaga, Spain

    • Inmaculada Doña
    •  & María J. Torres
  5. Department of Pharmacology, University of Extremadura, Caceres, Spain

    • Elena García-Martín
  6. Department of Clinical Biochemistry, Pharmacogenetics Unit, University Hospital of Salamanca, Salamanca, Spain

    • María Isidoro-García
  7. Allergy Department, Institute for Biomedical Research of Salamanca (IBSAL), Salamanca, Spain

    • María Isidoro-García
  8. Department of Medicine, Faculty of Medicine, University of Salamanca, Salamanca, Spain

    • María Isidoro-García
  9. Unitat d´Allergia, Servei de Pneumologia, Hospital Clinic, Universitat de Barcelona, Barcelona, Spain

    • Joan Bartra
  10. Institut d´Investigacions Biomediques August Pi I Sunyer (IDIBAPS), Barcelona, Spain

    • Joan Bartra
  11. Allergy Unit and Faculty of Dentistry, Virgen Macarena Hospital and University of Seville, Seville, Spain

    • David Ribas-Perez
  12. CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain

    • Carlos Flores
  13. Research Unit, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Spain

    • Carlos Flores
  14. Genomics Division, Instituto Tecnológico y de Energías Renovables (ITER), Tenerife, Spain

    • Carlos Flores

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The authors declare that they have no conflict of interest.

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Correspondence to José A. Cornejo-García.

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https://doi.org/10.1038/s41397-018-0038-0