TY - JOUR
T1 - Synergism interaction between genetic polymorphisms in drug metabolizing enzymes and NSAIDs on upper gastrointestinal haemorrhage :
T2 - a multicenter case-control study
AU - Vidal Guitart, Xavier
AU - Mallah, Narmeen
AU - Zapata-Cachafeiro, Maruxa
AU - Aguirre, Carmelo
AU - Ibarra-García, Eguzkiñe
AU - Palacios-Zabalza, Itziar
AU - Macías-García, Fernando
AU - Piñeiro-Lamas, María
AU - Vendrell Bosch, Lourdes
AU - Martin-Arias, Luis
AU - Sáinz-Gil, María
AU - Velasco-González, Verónica
AU - Bacariza-Cortiñas, Manuel
AU - Salgado, Angel
AU - Estany-Gestal, Ana
AU - Figueiras, Adolfo
PY - 2022
Y1 - 2022
N2 - 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
AB - 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
KW - Aspirin
KW - Genetic variation
KW - Interaction
KW - Non-steroidal anti-inflammatory drugs
KW - Upper gastrointestinal haemorrhage
UR - https://www.scopus.com/pages/publications/85124057333
U2 - 10.1080/07853890.2021.2016940
DO - 10.1080/07853890.2021.2016940
M3 - Article
C2 - 35114859
SN - 1365-2060
VL - 54
SP - 379
EP - 392
JO - Annals of Medicine
JF - Annals of Medicine
ER -