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Genetic polymorphisms associated with upper gastrointestinal bleeding: a systematic review.

Marcela Forgerini1, Rosa Camila Lucchetta1, Gustavo Urbano2

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Genetic variations influence the risk of non-variceal upper gastrointestinal bleeding (non-variceal UGIB), a severe drug reaction. Further research is needed to confirm these pharmacogenetic links for personalized medicine.

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Area of Science:

  • Pharmacogenetics
  • Gastroenterology
  • Drug Safety

Background:

  • Non-variceal upper gastrointestinal bleeding (non-variceal UGIB) is a significant adverse drug reaction.
  • Genetic susceptibility is hypothesized to underlie idiosyncratic non-variceal UGIB.
  • Understanding genetic factors can inform personalized medicine approaches.

Purpose of the Study:

  • To systematically review and assess the association between genetic polymorphisms and non-variceal UGIB.
  • To identify specific genetic variations potentially linked to non-variceal UGIB risk.
  • To evaluate the quality of existing evidence on pharmacogenetics of non-variceal UGIB.

Main Methods:

  • Systematic review of published literature.
  • Inclusion of 21 publications with 7134 participants.
  • Analysis of studies investigating genetic polymorphisms in patients exposed to NSAIDs, aspirin, and warfarin.

Main Results:

  • Thirteen studies examined genetic polymorphisms in relation to drug exposure.
  • Eight studies had methodological limitations, and only six clearly defined non-variceal UGIB as the outcome.
  • Associations were found between non-variceal UGIB risk and polymorphisms in genes related to platelet activation, angiogenesis, inflammation, and drug metabolism (e.g., NOS3, COX-2, CYP2C9, VKORC1).

Conclusions:

  • Several genetic polymorphisms are associated with the risk of non-variceal UGIB.
  • Methodological limitations in current studies hinder definitive conclusions.
  • Well-designed future studies are crucial for establishing robust pharmacogenetic evidence and advancing personalized medicine for non-variceal UGIB prevention.