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. cardiovasculares acetilsalicílico entanto RA . (RA) MEDLINEPubMed MEDLINE PubMed MEDLINE/PubMed Cochrane Scopus selecionados 29 destes 26 estabelecidos 2 casocontroles caso controles incluído rs rs112664 ITGA2, ITGA2 ITGA , (ITGA2) rs384278 PTGS1, PTGS1 PTGS rs2041 PTGS2 (PTGS2 rs591 ITGB3 ITGB (ITGB3 estudadas relevância 6 p< p (p 0,05 005 0 05 IC [IC 95% 95 artigo eles unânimes rs137109 P2RY1, P2RY1 PRY P RY (P2RY1) rs104564 MDR1, MDR1 MDR (MDR1) rs105193 rs775693 PLA2G7, PLA2G7 PLAG PLA G (PLA2G7) rs207174 HO1, HO1 HO (HO1) rs113188 rs452 TBXA2R, TBXA2R TBXAR TBXA R (TBXA2R) rs43447 ALOX12, ALOX12 ALOX (ALOX12) rs931504 ALOX5AP ALOXAP AP (ALOX5AP rs66 PON1, PON1 PON (PON1) ITGB3, rs224309 GP1BA, GP1BA GPBA GP BA (GP1BA) rs133034 (PTGS1 PTGS2. estudo destacamse destacam se populacionais expansão Portanto (RA rs11266 (ITGA2 rs38427 rs204 (PTGS rs59 (ITGB 0,0 00 9 rs13710 P2RY (P2RY1 rs10456 (MDR1 rs10519 rs77569 PLA2G (PLA2G7 rs20717 (HO1 rs11318 rs45 (TBXA2R rs4344 ALOX1 (ALOX12 rs93150 rs6 (PON1 rs22430 (GP1BA rs13303 rs1126 (ITGA rs3842 rs20 rs5 0, rs1371 (P2RY rs1045 (MDR rs1051 rs7756 (PLA2G rs2071 (HO rs1131 rs4 rs434 (ALOX1 rs9315 (PON rs2243 rs1330 rs112 rs384 rs2 rs137 rs104 rs105 rs775 rs207 rs113 rs43 (ALOX rs931 rs224 rs133 rs11 rs38 rs13 rs10 rs77 rs93 rs22 rs1 rs3 rs7 rs9
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. CVD . (CVD) acid vasoconstriction Nevertheless AR (AR) MEDLINEPubMed MEDLINE PubMed MEDLINE/PubMed Cochrane Scopus LILACS screened 29 26 criteria 2 casecontrol case included rs rs112664 ITGA2, ITGA2 ITGA , (ITGA2) rs384278 PTGS1, PTGS1 PTGS (PTGS1) rs2041 PTGS2, PTGS2 (PTGS2) rs591 ITGB3 ITGB (ITGB3 studied relevance 6 p< p (p 0.05 005 0 05 95 CI [CI] article them results rs137109 P2RY1, P2RY1 PRY P RY (P2RY1) rs104564 MDR1, MDR1 MDR (MDR1) rs105193 rs775693 PLA2G7, PLA2G7 PLAG PLA G (PLA2G7) rs207174 HO1, HO1 HO (HO1) rs113188 rs452 TBXA2R, TBXA2R TBXAR TBXA R (TBXA2R) rs43447 ALOX12, ALOX12 ALOX (ALOX12) rs931504 ALOX5AP, ALOX5AP ALOXAP AP (ALOX5AP) rs66 PON1, PON1 PON (PON1) ITGB3, rs224309 GP1BA, GP1BA GPBA GP BA (GP1BA) rs133034 PTGS2. limitations differences area Therefore (CVD (AR rs11266 (ITGA2 rs38427 (PTGS1 rs204 (PTGS2 rs59 (ITGB 0.0 00 9 [CI rs13710 P2RY (P2RY1 rs10456 (MDR1 rs10519 rs77569 PLA2G (PLA2G7 rs20717 (HO1 rs11318 rs45 (TBXA2R rs4344 ALOX1 (ALOX12 rs93150 (ALOX5AP rs6 (PON1 rs22430 (GP1BA rs13303 rs1126 (ITGA rs3842 (PTGS rs20 rs5 0. rs1371 (P2RY rs1045 (MDR rs1051 rs7756 (PLA2G rs2071 (HO rs1131 rs4 rs434 (ALOX1 rs9315 (PON rs2243 rs1330 rs112 rs384 rs2 rs137 rs104 rs105 rs775 rs207 rs113 rs43 (ALOX rs931 rs224 rs133 rs11 rs38 rs13 rs10 rs77 rs93 rs22 rs1 rs3 rs7 rs9