Sistema de Salut de Catalunya
Institut Català de la Salut
[Mallah N, Zapata-Cachafeiro M] Department of Preventive Medicine, University of Santiago de Compostela, Santiago de Compostela, Spain. Consortium for Biomedical Research in Epidemiology and Public Health (CIBER en Epidemiología Y Salud Pública CIBERESP), Carlos III Health Institute, Madrid, Spain. Health Research Institute of Santiago de Compostela (IDIS), Santiago de Compostela, Spain. [Aguirre C] Biocruces Bizkaia Health Research Institute, Pharmacotherapy Group, Bizkaia, Spain. University Hospital of Galdakao-Usansolo. Basque Country Pharmacovigilance Unit, Osakidetza, Spain. Pharmacology Department, Medicine and Nursing Faculty, University of the Basque Country, Barakaldo, Bizkaia, Spain. [Ibarra-García E] Biocruces Bizkaia Health Research Institute, Pharmacotherapy Group, Bizkaia, Spain. Pharmacy Department, Osakidetza Basque Health Service, Urduliz Hospital, Urduliz, Spain. [Palacios-Zabalza I] Biocruces Bizkaia Health Research Institute, Pharmacotherapy Group, Bizkaia, Spain. University Hospital of Galdakao-Usansolo. Basque Country Pharmacovigilance Unit, Osakidetza, Spain. [Macías García F] Department of Gastroenterology and Hepatology, University Hospital of Santiago de Compostela, Santiago de Compostela, Spain. [Ibáñez L, Vidal X, Vendrell L] Department of Pharmacology, Therapeutics and Toxicology, Clinical Pharmacology Service, Catalonian Institute of Pharmacology, Barcelona, Spain. Vall d’Hebron Hospital Universitari, Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain
Vall d'Hebron Barcelona Hospital Campus
2022-05-04T10:37:10Z
2022-05-04T10:37:10Z
2021-10-07
Gastroenterology; Pharmacogenetics
Gastroenterologia; Farmacogenètica
Gastroenterología; Farmacogenética
Bleeding in non-steroidal anti-inflammatory drug (NSAID) users limited their prescription. This first multicenter full case–control study (325 cases and 744 controls), explored the association of e-NOS intron 4 variable number tandem repeat (VNTR) polymorphism with upper gastrointestinal hemorrhage (UGIH) in NSAID exposed and unexposed populations and assessed any interaction between this polymorphism and NSAIDs. NSAID users carrying e-NOS intron 4 wild type genotype or VNTR polymorphism have higher odds of UGIH than those unexposed to NSAIDs [Odds Ratio (OR): 6.62 (95% Confidence Interval (CI): 4.24, 10.36) and OR: 5.41 (95% CI 2.62, 11.51), respectively], with no effect modification from VNTR polymorphism-NSAIDs interaction [Relative Excess Risk due to Interaction (RERI): −1.35 (95% CI −5.73, 3.03); Synergism Index (S): 0.77 (95% CI 0.31, 1.94)]. Similar findings were obtained for aspirin exposure. Non-aspirin NSAID users who carry e-NOS intron 4 VNTR polymorphism have lower odds of UGIH [OR: 4.02 (95% CI 1.85, 8.75) than those users with wild type genotype [OR: 6.52 (95% CI 4.09, 10.38)]; though the interaction estimates are not statistically significant [RERI: −2.68 (95% CI −6.67, 1.31); S: 0.53 (95% CI 0.18, 1.55)]. This exploratory study suggests that the odds of UGIH in NSAID or aspirin users does not modify according to patient´s e-NOS intron 4 genotype.
This work was supported by a grant from Instituto de Salud Carlos III [PI12/02414]/Plan Estatal de I + D + I 2012–2016; Fondo Europeo de Desarrollo Regional (FEDER); the Novartis, Pfizer and Dr Esteve pharmaceutical companies; the Health Research Fund/Fondo de Investigación Sanitaria [PI021512, PI021364, PI020661, PI021572]; Ministry of Health & Consumer Affairs, Spain [SAF2002-04057]; Galician Regional Authority, Spain [PGIDIT03PXIC20806PN]; Department of Health of the Basque Country [03/11092 and 11/111103]; and Fundacion vasca de innovacin e investigacin sanitarias [OSIBG19/002 and OSIBG18/105]. The genotyping service was carried out at CEGEN-PRB3-ISCIII; Instituto de Salud Carlos III and ERDF [PT17/0019, of the PE I + D + I 2013–2016].
Article
Published version
English
Hemorràgia gastrointestinal; Polimorfisme genètic; Antiinflamatoris no esteroïdals - Efectes secundaris; DISEASES::Digestive System Diseases::Gastrointestinal Diseases::Gastrointestinal Hemorrhage; PHENOMENA AND PROCESSES::Genetic Phenomena::Genetic Variation::Polymorphism, Genetic; CHEMICALS AND DRUGS::Chemical Actions and Uses::Pharmacologic Actions::Physiological Effects of Drugs::Peripheral Nervous System Agents::Sensory System Agents::Analgesics::Analgesics, Non-Narcotic::Anti-Inflammatory Agents, Non-Steroidal; Other subheadings::Other subheadings::Other subheadings::/adverse effects; ENFERMEDADES::enfermedades del sistema digestivo::enfermedades gastrointestinales::hemorragia gastrointestinal; FENÓMENOS Y PROCESOS::fenómenos genéticos::variación genética::polimorfismo genético; COMPUESTOS QUÍMICOS Y DROGAS::acciones y usos químicos::acciones farmacológicas::efectos fisiológicos de los fármacos::fármacos del sistema nervioso periférico::fármacos del sistema sensitivo::analgésicos::analgésicos no narcóticos::antiinflamatorios no esteroideos; Otros calificadores::Otros calificadores::Otros calificadores::/efectos adversos
Nature Research
Scientific Reports;11
https://doi.org/10.1038/s41598-021-99402-w
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
Articles científics - HVH [3440]
