A multicenter case-control study of the effect of e-nos VNTR polymorphism on upper gastrointestinal hemorrhage in NSAID users
Mallah, Narmeen (Instituto de Investigación Sanitaria de Santiago (IDIS))
Zapata-Cachafeiro, Maruxa (Universidad del País Vasco)
Ibarra-García, Eguzkiñe (Urduliz Hospital (Urduliz, País Basc))
Palacios-Zabalza, Itziar (Hospital de Galdakao (Usansolo, Biscaia))
Macías García, Fernando (Universidade de Santiago de Compostela)
Iglesias García, Júlio (Universidade de Santiago de Compostela)
Piñeiro-Lamas, María (Instituto de Investigación Sanitaria de Santiago (IDIS))
Ibáñez, Luisa (Hospital Universitari Vall d'Hebron)
Vidal Guitart, Xavier (Hospital Universitari Vall d'Hebron)
Vendrell, Lourdes (Hospital Universitari Vall d'Hebron)
Martin-Arias, Luís (Universidad de Valladolid)
Sáinz Gil, María (Universidad de Valladolid)
Salgado-Barreira, Ángel (Universidade de Santiago de Compostela)
Figueiras, Adolfo (Instituto de Investigación Sanitaria de Santiago (IDIS))
Universitat Autònoma de Barcelona

Date:	2021
Abstract:	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.
Grants:	Ministerio de Economía y Competitividad PI020661 Ministerio de Sanidad y Consumo SAF2002-04057 Ministerio de Economía y Competitividad PI12/02414
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Adult ; Aged ; Alleles ; Anti-Inflammatory Agents, Non-Steroidal ; Case-Control Studies ; Disease Susceptibility ; Female ; Gastrointestinal Hemorrhage ; Genetic Predisposition to Disease ; Genotype ; Humans ; Introns ; Male ; Middle Aged ; Minisatellite Repeats ; Nitric Oxide Synthase Type III ; Polymorphism, Genetic ; Risk Factors
Published in:	Scientific reports, Vol. 11 Núm. 1 (december 2021) , p. 19923, ISSN 2045-2322

DOI: 10.1038/s41598-021-99402-w
PMID: 34620931

9 p, 1.3 MB

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