Department of Drugs and Medicines, School of Pharmaceutical Sciences, São Paulo State University (UNESP), Araraquara, Brazil.
Department of Surgery, School of Medicine, University of São Paulo (USP), Ribeirão Preto, Brazil.
Pharmacogenomics J. 2021 Feb;21(1):20-36. doi: 10.1038/s41397-020-00185-6. Epub 2020 Sep 18.
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.
非静脉曲张性上消化道出血（非静脉曲张性 UGIB）是一种常见且严重的药物不良反应。有人提出，由于对非静脉曲张性 UGIB 的遗传易感性而导致的特发性反应。进行了系统评价，以评估遗传多态性与非静脉曲张性 UGIB 之间的关联。共纳入 21 篇文献和 7134 名参与者。13 项研究评估了非甾体抗炎药、低剂量阿司匹林和华法林暴露患者的遗传多态性。八项研究存在至少一个方法学问题。只有六项研究明确界定了所评估的结局是非静脉曲张性 UGIB。与非静脉曲张性 UGIB 风险相关的遗传多态性涉及血小板激活和聚集、血管生成、炎症过程和药物代谢（NOS3、COX-1；COX-2；PLA2G7；GP1BA；GRS；IL1RN；F13A1；CDKN2B-AS1；DPP6；TBXA2R；TNF-α；VKORC1；CYP2C9；和 AGT）。需要进一步进行设计良好的研究（例如，明确限制为非静脉曲张性 UGIB；适当选择参与者；以及调整混杂因素），以提供药物遗传学和个体化医学的有力证据。
