Genetic polymorphisms associated with upper gastrointestinal bleeding: a systematic review

Non-variceal upper gastrointestinal bleeding (non-variceal UGIB) is a frequent and severe adverse drug reaction. Idiosyncratic responses due to genetic susceptibility to non-variceal UGIB has been suggested. A systematic review was conducted to assess the association between genetic polymorphisms an...

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Bibliographic Details
Published in:The pharmacogenomics journal 2021-02, Vol.21 (1), p.20-36
Main Authors: Forgerini, Marcela, Lucchetta, Rosa Camila, Urbano, Gustavo, de Nadai, Tales Rubens, de Carvalho Mastroianni, Patrícia
Format: Article
Language:English
Subjects:
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Analysis
Angiogenesis
Aspirin
Biomedical and Life Sciences
Biomedicine
Bleeding
Cyclooxygenase-1
Cyclooxygenase-2
Disease susceptibility
Drug metabolism
Gastrointestinal bleeding
Gene Expression
Gene polymorphism
Genetic polymorphisms
Human Genetics
Inflammation
Interleukin 1
Nonsteroidal anti-inflammatory drugs
Oncology
Pharmacotherapy
Precision medicine
Psychopharmacology
Review Article
Systematic review
Tumor necrosis factor
Warfarin
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Summary:Non-variceal upper gastrointestinal bleeding (non-variceal UGIB) is a frequent and severe adverse drug reaction. Idiosyncratic responses due to genetic susceptibility to non-variceal UGIB has been suggested. A systematic review was conducted to assess the association between genetic polymorphisms and non-variceal UGIB. Twenty-one publications and 7134 participants were included. Thirteen studies evaluated genetic polymorphism in patients exposed to non-steroidal anti-inflammatory drugs, low-dose aspirin, and warfarin. Eight studies present at least one methodological problem. Only six studies clearly defined that the outcome evaluated was non-variceal UGIB. Genetic polymorphisms involved in platelet activation and aggregation, angiogenesis, inflammatory process, and drug metabolism were associated with risk of non-variceal UGIB ( NOS3 ,  COX-1 ; COX-2 ; PLA2G7 ; GP1BA ; GRS ; IL1RN ; F13A1 ; CDKN2B-AS1 ; DPP6 ; TBXA2R ; TNF-alpha ; VKORC1 ; CYP2C9; and AGT ). Further well-designed studies are needed (e.g., clear restriction to non-variceal UGIB; proper selection of participants; and adjustment of confounding factors) to provide strong evidence for pharmacogenetic and personalized medicine.
ISSN:1470-269X
1473-1150
DOI:10.1038/s41397-020-00185-6