Repositorio UFRO · Omeka S

Genetic Variant ABCC1 rs45511401 Is Associated with Increased Response to Statins in Patients with Familial Hypercholesterolemia

Primer Autor	Dagli-Hernandez, Carolina
Co-autores	Borges, Jessica Bassani Rodrigues Marcal, Elisangela da Silva Costa de Freitas, Renata Caroline Mori, Augusto Akira Goncalves, Rodrigo Marques Faludi, Andre Arpad de Oliveira, Victor Fernandes Ferreira, Glaucio Monteiro Bastos, Gisele Medeiros Zhou, Yitian Lauschke, Volker M. Cerda, Alvaro Hirata, Mario Hiroyuki Crespo Hirata, Rosario Dominguez
Título	Genetic Variant ABCC1 rs45511401 Is Associated with Increased Response to Statins in Patients with Familial Hypercholesterolemia
Editorial	MDPI
Revista	PHARMACEUTICS
Lenguaje	en
Resumen	Statins are the first-line treatment for familial hypercholesterolemia (FH), but response is highly variable due to genetic and nongenetic factors. Here, we explored the association between response and genetic variability in 114 Brazilian adult FH patients. Specifically, a panel of 84 genes was analyzed by exon-targeted gene sequencing (ETGS), and the functional impact of variants in pharmacokinetic (PK) genes was assessed using an array of functionality prediction methods. Low-density lipoprotein cholesterol (LDL-c) response to statins (reduction >= 50%) and statin-related adverse event (SRAE) risk were assessed in carriers of deleterious variants in PK-related genes using multivariate linear regression analyses. Fifty-eight (50.8%) FH patients responded to statins, and 24 (21.0%) had SRAE. Results of the multivariate regression analysis revealed that ABCC1 rs45511401 significantly increased LDL-c reduction after statin treatment (p < 0.05). In silico analysis of the amino-acid change using molecular docking showed that ABCC1 rs45511401 possibly impairs statin efflux. Deleterious variants in PK genes were not associated with an increased risk of SRAE. In conclusion, the deleterious variant ABCC1 rs45511401 enhanced LDL-c response in Brazilian FH patients. As such, this variant might be a promising candidate for the individualization of statin therapy.
Tipo de Recurso	artículo original
doi	10.3390/pharmaceutics14050944
Formato Recurso	PDF
Palabras Claves	statin lipid response familial hypercholesterolemia pharmacogenetics adverse drug events myalgia lipid-lowering drugs ATORVASTATIN THERAPY TOXICITY ABCB1 PHARMACOGENETICS POLYMORPHISMS CHOLESTEROL DIAGNOSIS EFFICACY IMPACT
Ubicación del archivo	http://dx.doi.org/10.3390/pharmaceutics14050944
Categoría OCDE	Farmacología y farmacia
Materias	estatina respuesta lipídica hipercolesterolemia familiar farmacogenética eventos adversos a medicamentos mialgia medicamentos hipolipemiantes ATORVASTATIN TERAPIA TOXICIDAD ABCB1 FARMACOGENETICA POLIMORFISMOS COLESTEROL DIAGNÓSTICO EFICACIA IMPACTO
Disciplinas de la OCDE	Farmacología y Farmacia Genética Humana Biotecnología Relacionada con la Salud
Título de la cita (Recomendado-único)	Genetic Variant ABCC1 rs45511401 Is Associated with Increased Response to Statins in Patients with Familial Hypercholesterolemia
Identificador del recurso (Mandatado-único)	artículo original
Versión del recurso (Recomendado-único)	version publicada
License	CC BY 4.0
Condición de la licencia (Recomendado-repetible)	CC BY 4.0
Derechos de acceso	acceso abierto
Access Rights	acceso abierto
Id de Web of Science	WOS:000803486400001