Genetic variant ABCC1 rs45511401 is associated with increased response to statins in patients with familial hypercholesterolemia
Pharmaceutics
; 14(5): 1-20, Apr.2022. tab, ilus, graf
Artículo
en Inglés
| CONASS, Sec. Est. Saúde SP, SESSP-IDPCPROD, Sec. Est. Saúde SP
| ID: biblio-1371140
Biblioteca responsable:
BR79.1
ABSTRACT
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.
Texto completo:
Disponible
Colección:
Bases de datos nacionales
/
Brasil
Base de datos:
CONASS
/
Sec. Est. Saúde SP
/
SESSP-IDPCPROD
Asunto principal:
Farmacogenética
/
Inhibidores de Hidroximetilglutaril-CoA Reductasas
/
Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos
Tipo de estudio:
Estudio pronóstico
/
Factores de riesgo
Idioma:
Inglés
Revista:
Pharmaceutics
Año:
2022
Tipo del documento:
Artículo
Institución/País de afiliación:
Institute Dante Pazzanese of Cardiology/BR
/
Karolinska Institutet/SE
/
Universidad de La Frontera/CL
/
University of Sao Paulo/BR