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Genetic polymorphisms associated with upper gastrointestinal bleeding: a systematic review

The Pharmacogenomics Journal volume 21, pages 20–36 (2021)Cite this article

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Abstract

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.

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Fig. 1: A Study selection.

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Acknowledgements

São Paulo Research Foundation (FAPESP) [grant number 2017/24193-3; 2018/07501-9], Conselho Nacional de Desenvolvimento Tecnológico (CNPq) [grant number 401060/2014-4], and Programa de Apoio ao Desenvolvimento Cientifico (PADC) of School of Pharmaceutical Sciences of São Paulo State University (UNESP), Brazil. This study was also financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior–Brasil (CAPES, Finance Code 001). These funders had no role in any of the phases of the study (i.e., study design, data collection, data analysis, interpretation, writing of the report, and responsibility for submission).

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  1. Department of Drugs and Medicines, School of Pharmaceutical Sciences, São Paulo State University (UNESP), Araraquara, Brazil

    Marcela Forgerini, Rosa Camila Lucchetta & Patrícia de Carvalho Mastroianni

  2. Department of Surgery, School of Medicine, University of São Paulo (USP), Ribeirão Preto, Brazil

    Gustavo Urbano

  3. Department of Public Health, Bauru School of Dentistry, University of São Paulo (USP), Bauru, Brazil

    Tales Rubens de Nadai

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Forgerini, M., Lucchetta, R.C., Urbano, G. et al. Genetic polymorphisms associated with upper gastrointestinal bleeding: a systematic review. Pharmacogenomics J 21, 20–36 (2021). https://doi.org/10.1038/s41397-020-00185-6

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