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Polymorphisms in CEP68 gene associated with risk of immediate selective reactions to non-steroidal anti-inflammatory drugs.

Pharmacogenomics J.2019 Apr;19(2):191-199. Epub 2018 Aug 10
James R Perkins 1 , Marialbert Acosta-Herrera 2 , María C Plaza-Serón 3 , Raquel Jurado-Escobar 3 , Inmaculada Doña 4 , Elena García-Martín 5 , María Isidoro-García 6 , Joan Bartra 7 , David Ribas-Perez 8 , Cristobalina Mayorga 1 , María J Torres 4 , Carlos Flores 9 , José A Cornejo-García 10
James R Perkins 1 , Marialbert Acosta-Herrera 2 , María C Plaza-Serón 3 , Raquel Jurado-Escobar 3 , Inmaculada Doña 4 , Elena García-Martín 5 , María Isidoro-García 6 , Joan Bartra 7 , David Ribas-Perez 8 , Cristobalina Mayorga 1 , María J Torres 4 , Carlos Flores 9 , José A Cornejo-García 10
+ et al

[No authors listed]

Author information
  • 1 ARADyAL Network. Instituto de Salud Carlos III, Madrid, Spain.
  • 2 Instituto de Parasitología y Biomedicina López-Neyra, IPBLN-CSIC, P.T.S., Granada, Spain.
  • 3 Research Laboratory, IBIMA, Regional University Hospital of Malaga, UMA, Malaga, Spain.
  • 4 Allergy Unit, IBIMA, Regional University Hospital of Malaga, UMA, Malaga, Spain.
  • 5 Department of Pharmacology, University of Extremadura, Caceres, Spain.
  • 6 Department of Medicine, Faculty of Medicine, University of Salamanca, Salamanca, Spain.
  • 7 Institut d´Investigacions Biomediques August Pi I Sunyer (IDIBAPS), Barcelona, Spain.
  • 8 Allergy Unit and Faculty of Dentistry, Virgen Macarena Hospital and University of Seville, Seville, Spain.
  • 9 Genomics Division, Instituto Tecnológico y de Energías Renovables (ITER), Tenerife, Spain.
  • 10 ARADyAL Network. Instituto de Salud Carlos III, Madrid, Spain. josea.cornejo@ibima.eu.

摘要


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.