Genetic determinants of gastrointestinal bleeding associated with the use of ASA as an antiplalet agent: a case-control study

• Grant number: 17/24193-3
• Support Opportunities: Regular Research Grants
• Duration: June 01, 2020 - May 31, 2023
• Field of knowledge: Health Sciences - Pharmacy
• Principal Investigator: Patricia de Carvalho Mastroianni
• Grantee: Patricia de Carvalho Mastroianni
• Host Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil
• Associated researchers: Adolfo Figueiras ; Gustavo Urbano ; Marcela Forgerini ; Maria Teresa Ferreira Herdeiro ; Tales Rubens de Nadai

Abstract

Gastrointestinal Haemorrhages (GIHs) are one of the most frequent and severe adverse drugreactions. The idiosyncratic responses with respect to the haemorrhages observed inindividuals consuming acetylsalicylic acid (ASA) as an antiplatelet agent could be due to thepresence of genetic variants described in the genes that encoding enzyme targets involved inthe pharmacological and pharmacodynamic activity of AAS metabolismo: cyclooxygenase(cox)-1, Nitric oxide synthases (eNOS), cytochrome p450 (CYP2C9); p-glycoprotein(ABCB1) and Vitamin K epOxide Reductase Complex (VKORC1). The objective of thisstudy is to asses the risk of GIH by ASA consumption related to the presence of these geneticvariants. METHOD: An incident case-control study will be performed. Individuals (n=200)suffering ulcer perforation or upper gastrointestinal bleeding, diagnosed by endoscopy, willbe considered cases. 600 controls will be recruited from the preoperative unit to undergotrivial surgeries of painless processes. Both the cases and the controls will be extensivelyinterviewed, and ASA consumption and variables of control and adjustment will be evaluated.SNP genotyping will be identified by real-time polymerase chain reaction (PCR) with theTaqPath ProAmp assay (Applied Biosystems®). A pooled analysis will be performed with thedata of the previous study and with the current one, constructing mixed linear models todependent binomial-type variables. (AU)

Scientific publications

(5)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

FORGERINI, MARCELA; LUCCHETTA, ROSA CAMILA; URBANO, GUSTAVO; DE NADAI, TALES RUBENS; DE CARVALHO MASTROIANNI, PATRICIA. Genetic polymorphisms associated with upper gastrointestinal bleeding: a systematic review. PHARMACOGENOMICS JOURNAL, v. 21, n. 1, p. 20-36, FEB 2021. (18/07501-9, 17/24193-3)

MARCELA FORGERINI; GUSTAVO URBANO; TALES RUBENS DE NADAI; MARUXA ZAPATA-CACHAFEIRO; RAFAEL KEMP; PATRÍCIA DE CARVALHO MASTROIANNI. Perfil epidemiológico de pacientes com hemorragia gastrointestinal alta não varicosa decorrente de doença péptica em um hospital brasileiro terciário de referência. Arq. Gastroenterol., v. 58, n. 2, p. 202-209, 2021-06-25. (18/07501-9, 17/24193-3)

FORGERINI, MARCELA; URBANO, GUSTAVO; DE NADAI, TALES RUBENS; ZANELLI, CLESLEI FERNANDO; VALENTINI, SANDRO ROBERTO; MASTROIANNI, PATRICIA DE CARVALHO. VNTR Polymorphism in Intron 4 of the eNOS Gene and the Risk of Gastrointestinal Bleeding: A Case-control Study. JOURNAL OF GASTROINTESTINAL AND LIVER DISEASES, v. 31, n. 2, p. 8-pg., 2022-04-06. (18/07501-9, 17/24193-3)

FORGERINI, MARCELA; URBANO, GUSTAVO; NADAI, TALES RUBENS DE; BATAH, SABRINA SETEMBRE; FABRO, ALEXANDRE TODOROVIC; MASTROIANNI, PATRICIA DE CARVALHO. Genetic Variants in PTGS1 and NOS3 Genes Increase the Risk of Upper Gastrointestinal Bleeding: A Case-Control Study. FRONTIERS IN PHARMACOLOGY, v. 12, JUL 5 2021. (19/19591-5, 17/24193-3, 18/07501-9)

FORGERINI, MARCELA; URBANO, GUSTAVO; DE NADAI, TALES RUBENS; BATAH, SABRINA SETEMBRE; FABRO, ALEXANDRE TODOROVIC; MASTROIANNI, PATRICIA DE CARVALHO. The role of CYP2C9*2, CYP2C9*3 and VKORC1-1639 variants on the susceptibility of upper gastrointestinal bleeding: A full case-control study. JOURNAL OF PHARMACY AND PHARMACEUTICAL SCIENCES, v. 26, p. 13-pg., 2023-01-30. (18/07501-9, 17/24193-3)