RT Journal Article
T1 Influence of Polymorphisms Involved in Platelet Activation and Inflammatory Response on Aspirin-Related Upper Gastrointestinal Bleeding: A Case-Control Study
A1 Mallah, Narmeen
A1 Zapata Cachafeiro, Maruxa
A1 Aguirre, Carmelo
A1 Ibarra-García, Eguzkiñe
A1 Palacios-Zabalza, itziar
A1 Macías-García, Fernando
A1 Domínguez Muñoz, Juan Enrique
A1 Piñeiro Lamas, María
A1 Ibañez, Luisa
A1 Vidal, Xavier
A1 Luis, Vendrell
A1 Velasco-González, Verónica
A1 Figueiras Guzmán, Adolfo
A1 Sáinz-Gil, María
K1 Aspirin
K1 Upper gastrointestinal haemorrhage
K1 Genetic polymorphism
K1 Pharmacogenomics
K1 Platelet
K1 Interaction
AB BackgroundDespite the wide benefits of aspirin and its cost-effectiveness, aspirin prescriptions have been reduced due to idiosyncratic responses in susceptible individuals. Low-dose aspirin and single-nucleotide polymorphisms (SNPs) are independently associated with increased risk of gastrointestinal hemorrhage; however, to-date, no studies investigated the SNP-aspirin interaction effect on upper gastrointestinal hemorrhage (UGIH). Therefore, we aimed to evaluate the role of 25 SNPs in multiple genes involved in platelet activation, angiogenesis and inflammatory response in aspirin-related UGIH.MethodsA multicenter, full case–control study was conducted in patients exposed and unexposed to aspirin. Three hundred twenty-six cases diagnosed with UGIH were matched with 748 controls (1:3) by age, gender, health center, and recruitment date. Only adults of European origin were included. Participants were stratified by aspirin exposure and genotype [(Aspirin(−), wild-type), (Aspirin(+), wild-type), (Aspirin(+), genetic variation), (Aspirin(−), genetic variation)]. For each SNP, the Odds Ratio of UGIH and their 95% confidence intervals were estimated in each subgroup by using the generalized linear mixed models for dependent binomial variables. SNP-aspirin interaction effect was estimated through Relative Excess Risk due to Interaction (RERI) measures.ResultsWe observed two categories of SNPs that might modify the risk magnitude of UGIH in aspirin consumers. Seven SNPs (rs1387180 A > G, rs2238631 T > C, rs1799964 T > C, rs5050 T > C/T > G, rs689466 T > C, rs1799983 T > A/T > G, and rs7756935 C > A) were “positive modifiers” associated with an excess of risk from aspirin exposure and carrying that genetic variation (1.75 ≤ RERI ≤ 4.95). On the contrary, the following nine SNPs (rs2243086 G > T, rs1131882 G > A, rs4311994 C > T, rs10120688 G > A, rs4251961 T > C, rs3778355 G > C, rs1330344 C > T, rs5275 A > G/A > T, and rs3779647 C > T) were “negative modifiers” and associated with a reduced risk in aspirin users (−2.74 ≤ RERI ≤ −0.95).ConclusionThis preliminary study suggests that polymorphisms in genes involved in platelets activity, angiogenesis and inflammatory response might modify the risk of aspirin-related UGIH. Further studies with larger sample size and in different populations are needed to confirm our findings. If confirmed, this might have great impact on public health, thanks to aspirin’s prophylactic properties in diseases of high incidence and severity.
PB Frontiers
YR 2020
FD 2020-06-09
LK http://hdl.handle.net/10347/32817
UL http://hdl.handle.net/10347/32817
LA eng
NO Mallah N, Zapata-Cachafeiro M, Aguirre C, Ibarra-García E, Palacios-Zabalza I, Macías-García F, Domínguez-Muñoz JE, Piñeiro-Lamas M, Ibáñez L, Vidal X, Vendrell L, Martin-Arias L, Sáinz-Gil M, Velasco-González V, Figueiras A. Influence of Polymorphisms Involved in Platelet Activation and Inflammatory Response on Aspirin-Related Upper Gastrointestinal Bleeding: A Case-Control Study. Front Pharmacol. 2020 Jun 9;11:860.
NO 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, and 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); Fundacion Vasca de innovacion e investigacion 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).
DS Minerva
RD 3 may 2026