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CC BY 4.0 · Arq Neuropsiquiatr 2023; 81(01): 062-073
DOI: 10.1055/s-0042-1758445
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Impact of pharmacogenetics on aspirin resistance: a systematic review

Impacto da farmacogenética na resistência à aspirina: uma revisão sistemática
Gustavo Figueiredo da Silva 
1   Universidade da Região de Joinville, Departamento de Medicina, Joinville SC, Brazil
,
Bruno Mattei Lopes 
1   Universidade da Região de Joinville, Departamento de Medicina, Joinville SC, Brazil
,
Vinicius Moser 
1   Universidade da Região de Joinville, Departamento de Medicina, Joinville SC, Brazil
,
Leslie Ecker Ferreira 
1   Universidade da Região de Joinville, Departamento de Medicina, Joinville SC, Brazil
2   Universidade da Região de Joinville, Joinville Stroke Biobank, Joinville SC, Brazil
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Abstract

Background Pharmacogenetics promises better control of diseases such as cardiovascular disease (CVD). Acetylsalicylic acid, aspirin, prevents the formation of an activating agent of platelet aggregation and vasoconstriction, and it is used to prevent CVD. Nevertheless, patients may have treatment failure due to genetic variants that modify the metabolism of the drug causing aspirin resistance (AR).

Objectives To realize a systematic literature review to determine the impact of genetic variants on AR.

Methods Articles published in the MEDLINE/PubMed, Cochrane, Scopus, LILACS, and SCIELO databases were systematically screened. A total of 290 articles were identified and 269 articles were excluded because they did not comply with the previously established inclusion criteria. A total of 20 case-control studies and 1 cohort was included.

Results The genetic variants rs1126643 (ITGA2), rs3842787 (PTGS1), rs20417 (PTGS2), and rs5918 (ITGB3) were the most studied. As for relevance, of the 64 genetic variants evaluated by the articles, 14 had statistical significance (p < 0.05; 95% confidence interval [CI]) in at least one article. Among them, the following have had unanimous results: rs1371097 (P2RY1), rs1045642 (MDR1), rs1051931 and rs7756935 (PLA2G7), rs2071746 (HO1), rs1131882 and rs4523 (TBXA2R), rs434473 (ALOX12), rs9315042 (ALOX5AP), and rs662 (PON1), while these differ in real interference in AR: rs5918 (ITGB3), rs2243093 (GP1BA), rs1330344 (PTGS1), and rs20417 (PTGS2). As study limitations, we highlight the nonuniform methodologies of the analyzed articles and population differences.

Conclusion It is noteworthy that pharmacogenetics is an expanding area. Therefore, further studies are needed to better understand the association between genetic variants and AR.

Resumo

Antecedentes A farmacogenética promete melhorar o controle de doenças como as cardiovasculares. O ácido acetilsalicílico, a aspirina, previne a formação de um agente ativador da agregação plaquetária e vasoconstrição e é usado na prevenção de tais doenças. No entanto, os pacientes podem ter falha no tratamento devido a variantes genéticas que modificam o metabolismo da droga causando resistência à aspirina (RA).

Objetivos Realizar uma revisão sistemática da literatura para determinar o impacto das variantes genéticas na resistência à aspirina.

Métodos Artigos publicados nos bancos de dados MEDLINE/PubMed, Cochrane, Scopus, LILACS e SCIELO foram sistematicamente selecionados. Foram identificados 290 artigos e, destes, 269 artigos foram excluídos por não atenderem aos critérios de inclusão previamente estabelecidos. Um total de 20 estudos caso-controles e 1 coorte foi incluído.

Resultados As variantes genéticas rs1126643 (ITGA2), rs3842787 (PTGS1), rs20417 (PTGS2) e rs5918 (ITGB3) foram as mais estudadas. Quanto à relevância, das 64 variantes genéticas avaliadas pelos artigos, 14 tiveram significância estatística (p < 0,05; intervalo de confiança [IC] de 95%) em pelo menos um artigo. Entre eles, os seguintes tiveram resultados unânimes: rs1371097 (P2RY1), rs1045642 (MDR1), rs1051931 e rs7756935 (PLA2G7), rs2071746 (HO1), rs1131882 e rs4523 (TBXA2R), rs434473 (ALOX12), rs9315042 (ALOX5AP) e rs662 (PON1), enquanto estes diferiram na interferência real na RA: rs5918 (ITGB3), rs2243093 (GP1BA), rs1330344 (PTGS1) e rs20417 (PTGS2). Como limitações do estudo, destacam-se as metodologias não uniformes dos artigos analisados e as diferenças populacionais.

Conclusão Vale ressaltar que a farmacogenética é uma área em expansão. Portanto, mais estudos são necessários para entender melhor a associação entre variantes genéticas e RA.

Keywords

Pharmacogenetics - Aspirin - Genetic Variation

Palavras-chave

Farmacogenética - Aspirina - Variação Genética

Authors' Contributions

All authors contributed to data collection, information organization and article writing. All authors approved the final version.




Publikationsverlauf

Eingereicht: 28. September 2021

Angenommen: 22. November 2021

Artikel online veröffentlicht:
14. März 2023

© 2023. Academia Brasileira de Neurologia. This is an open access article published by Thieme under the terms of the Creative Commons Attribution 4.0 International License, permitting copying and reproduction so long as the original work is given appropriate credit (https://creativecommons.org/licenses/by/4.0/)

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