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
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Colección Publicaciones Científicas
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