Synergism interaction between genetic polymorphisms in drug metabolizing enzymes and NSAIDs on upper gastrointestinal haemorrhage : a multicenter case-control study
Mallah, Narmeen (Centro de Investigación Biomédica en Red de Enfermedades Respiratorias)
Zapata-Cachafeiro, Maruxa (Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública)
Aguirre, Carmelo (Universidad del País Vasco)
Ibarra-García, Eguzkiñe (Hospital de Urduliz Alfredo Espinosa)
Palacios-Zabalza, Itziar (Hospital de Galdakao (Usansolo, Biscaia))
Macías-García, Fernando (Complejo Hospitalario Universitario 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 Bosch, Lourdes (Hospital Universitari Vall d'Hebron)
Martin-Arias, Luis (Universidad de Valladolid)
Sáinz-Gil, María (Universidad de Valladolid)
Velasco-González, Verónica (Universidad de Valladolid)
Bacariza-Cortiñas, Manuel (Centro de Saúde de Vite)
Salgado, Angel (University of Santiago de Compostela)
Estany-Gestal, Ana (Instituto de Investigación Sanitaria de Santiago (IDIS))
Figueiras, Adolfo (Instituto de Investigación Sanitaria de Santiago (IDIS))
Universitat Autònoma de Barcelona

Data:	2022
Resum:	Interindividual genetic variations contribute to differences in patients' response to drugs as well as to the development of certain disorders. Patients who use non-steroidal anti-inflammatory drugs (NSAIDs) may develop serious gastrointestinal disorders, mainly upper gastrointestinal haemorrhage (UGIH). Studies about the interaction between NSAIDs and genetic variations on the risk of UGIH are scarce. Therefore, we investigated the effect of 16 single nucleotide polymorphisms (SNPs) involved in drug metabolism on the risk of NSAIDs-induced UGIH. We conducted a multicenter case-control study of 326 cases and 748 controls. Participants were sub-grouped into four categories according to NSAID exposure and genetic profile. We estimated odds ratios (ORs) and their 95% confidence intervals (CI) using generalized linear mixed models for dependent binomial variables and then calculated the measures of interaction, synergism index (S), and relative excess risk due to interaction (RERI). We undertook stratified analyses by the type of NSAID (aspirin, non-aspirin). We observed an excess risk of UGIH due to an interaction between any NSAID, non-aspirin NSAIDs or aspirin and carrying certain SNPs. The greatest excess risk was observed for carriers of: rs2180314:C>G [any NSAID: S = 3. 30 (95%CI: 1. 24-8. 80), RERI = 4. 39 (95%CI: 0. 70-8. 07); non-aspirin NSAIDs: S = 3. 42 (95%CI: 1. 12-10. 47), RERI = 3. 97 (95%CI: 0. 44-7. 50)], and rs4809957:A>G [any NSAID: S = 2. 11 (95%CI: 0. 90-4. 97), RERI = 3. 46 (95%CI: −0. 40-7. 31)]. Aspirin use by carriers of rs6664:C>T is also associated with increased risk of UGIH [OR: 2. 22 (95%CI: 0. 69-7. 17) vs. OR: 7. 72 (95%CI: 2. 75-21. 68)], yet larger sample size is needed to confirm this observation. The joint effect of the SNPs s2180314:C>G and rs4809957:A>G and NSAIDs are more than three times higher than the sum of their individual effects. Personalized prescriptions based on genotyping would permit a better weighing of risks and benefits from NSAID consumption.
Ajuts:	Instituto de Salud Carlos III PI12/0241 Instituto de Salud Carlos III PT17/001 Ministerio de Sanidad y Consumo SAF2002-04057
Drets:	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.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Aspirin ; Genetic variation ; Interaction ; Non-steroidal anti-inflammatory drugs ; Upper gastrointestinal haemorrhage
Publicat a:	Annals of Medicine, Vol. 54 (february 2022) , p. 379-392, ISSN 1365-2060

DOI: 10.1080/07853890.2021.2016940
PMID: 35114859

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