Influência de variantes polimórficas de CYP2C19 na aterosclerose

• Autor(a) principal: Costa, Iasmim Ribeiro da
• Data de Publicação: 2019
• Tipo de documento: Tese
• Idioma: por
• Título da fonte: Repositório Institucional da UFG
• dARK ID: ark:/38995/00130000092dm
• Texto Completo: http://repositorio.bc.ufg.br/tede/handle/tede/10092
• topic: Aterosclerose; CYP2C19; Clopidogrel; Polimorfismo; Reestenose; Stent; Atherosclerosis; CYP2C19; Clopidogrel; Polymorphism; Restenosis; Stent; FARMACIA::FARMACOGNOSIA

The cytochrome P450 (CYP) family enzymes are responsible for detoxification of the organism, as well as acting on the biotransformation of various drugs. Atherosclerosis patients undergoing interventional procedures are at increased risk for thrombus formation, and the use of platelet antiaggregants is required. Clopidogrel antiplatelet is a prodrug that needs to be activated by CYP family enzymes. Polymorphisms of this family, besides being related to atherogenesis, may influence the response to this drug. This study aimed to verify the possible association of CYP2C19 genotypes in response to clopidogrel. Two hundred and ninety-nine DNA samples from patients with and without atherosclerosis for the CYP2C19 * 2, * 3 and * 17 polymorphism were analyzed by ARMS-PCR and PCR-RFLP techniques. Regarding the atherogenesis process, the presence of two polymorphic * 2 alleles or one * 3 allele may have influenced the development of atherosclerosis. Allele 17 functioned as a protective factor, even in the presence of a * 2 or * 3. The combination of two mutated * 2 alleles and the presence of * 3 influenced the development of atherosclerosis, even when * 17 was present. By evaluating CYP2C19 polymorphisms and their association with disease progression, the need for stenting, generated somewhat contradictory results. Regarding response to clopidogrel and combinations of CYP2C19 polymorphisms, we found that the poor metabolizing phenotype (* 1 * 2 / * 1 * 3 / * 1 / * 17) was more prevalent in the restenosis group, reflecting the lack of activation of clopidogrel by the enzyme CYP. Although there are contradictory studies regarding the response to clopidogrel in patients with loss of function polymorphisms for the CYP2C19 gene, we found that allele 2 not only influences the atherogenesis process, but also influences the response to clopodigrel.