CYP2C9 variants as a risk modifier of NSAID-related gastrointestinal bleeding : a case-control study
Figueiras, Adolfo (Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública)
Estany-Gestal, Ana (Universidad de Santiago de Compostela. Departamento de Medicina Preventiva y Salud Pública)
Aguirre, Carmelo (Hospital de Galdakao (Usansolo, Biscaia))
Ruiz, Borja (Department of Pharmacology, Basque Country University School of Medicine)
Vidal Guitart, Xavier (Universitat Autònoma de Barcelona. Departament de Farmacologia, de Terapèutica i de Toxicologia)
Carvajal, Alfonso (Universidad de Valladolid)
Salado, Inés (Universidad de Valladolid)
Salgado-Barreira, Angel (Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública)
Rodella, Luca (Service of Digestive Endoscopy)
Moretti, Ugo (University Hospital of Verona (Itàlia))
Ibáñez, Luisa (Universitat Autònoma de Barcelona. Departament de Farmacologia, de Terapèutica i de Toxicologia)
Vall d'Hebron Institut de Recerca (VHIR)
Fundació Institut Català de Farmacologia

Data:	2016
Resum:	We conducted a multicenter, case-control study in which cases were patients aged more than 18 years with a diagnosis of UGIB, and controls were matched (1 : 3) by sex, age, date of admission, and hospital. Exposure was defined as the mean number of defined daily doses (DDDs) of NSAIDs metabolized by CYP2C9 in the week preceding the index date. Three DDD categories were defined (0, ≤0. 5, and >0. 5). Exposure was constructed taking both NSAID use and CYP2C9 polymorphisms into account. Patients of non-European origin were excluded from the analysis. A total of 577 cases and 1343 controls were finally included in the analysis: 103 cases and 89 controls consumed NSAIDs metabolized by CYP2C9, and 88 cases and 177 controls were CYP2C9*3 carriers. The adjusted odds ratios (aORs) of UGIB associated with the CYP2C9*2 and wild-type alleles proved to be similar [OR=8. 79 (4. 50-17. 17) and 10. 15 (2. 92-35. 35), respectively] and lower than those of the CYP2C9*3 allele [aOR=18. 07 (6. 34-51. 53)] for consumers taking more than 0. 5 DDDs of NSAIDs metabolized by CYP2C9. Grouping genotypes into carriers and noncarriers of the CYP2C9*3 variant resulted in aORs of 16. 92 (4. 96-57. 59) for carriers and 9. 72 (4. 55-20. 76) for noncarriers, where DDDs were greater than 0. 5. The presence of the CYP2C9*3 variant increases the risk for UGIB associated with NSAID for DDDs greater than 0. 5. The presence of the CYP2C9*2 allele shows no such effect.
Ajuts:	Instituto de Salud Carlos III PI12-02414 Ministerio de Ciencia e Innovación SAF2002-04057
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	CYP2C9*2 ; CYP2C9*3 ; Gastrointestinal hemorrhage ; NSAID
Publicat a:	Pharmacogenetics and Genomics, Vol. 26 (january 2016) , p. 66-73, ISSN 1744-6880

DOI: 10.1097/FPC.0000000000000186
PMID: 26544900

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