2026-04-17T04:29:54Zhttps://recercat.cat/oai/request

oai:recercat.cat:11351/74772025-10-24T08:24:47Zcom_2072_378070com_2072_378040col_2072_378092

A multicenter case–control study of the effect of e-nos VNTR polymorphism on upper gastrointestinal hemorrhage in NSAID users Mallah, Narmeen Zapata‑Cachafeiro, Maruxa Aguirre, Carmelo Ibarra‑García, Eguzkiñe Palacios-Zabalza, Itziar Macías García, Fernando Ibáñez, Luisa Vidal Guitart, Xavier Vendrell Bosch, Lourdes 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 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]. 2025-10-24T08:24:47Z 2025-10-24T08:24:47Z 2025-10-24T08:24:47Z 2022-05-04T10:37:10Z 2022-05-04T10:37:10Z 2021-10-07 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion http://hdl.handle.net/11351/7477 Scientific Reports;11 https://doi.org/10.1038/s41598-021-99402-w Attribution 4.0 International http://creativecommons.org/licenses/by/4.0/ info:eu-repo/semantics/openAccess Nature Research Scientia