The effect of genetic variation in PCSK9 on the LDL-cholesterol response to statin therapy.
Pharmacogenomics J
; 17(2): 204-208, 2017 03.
Article
em En
| MEDLINE
| ID: mdl-26902539
ABSTRACT
Statins (HMG-CoA reductase inhibitors) lower low-density lipoprotein cholesterol (LDL-C) and prevent cardiovascular disease. However, there is wide individual variation in LDL-C response. Drugs targeting proprotein convertase subtilin/kexin type 9 (PCSK9) lower LDL-C and will be used with statins. PCSK9 mediates the degradation of LDL receptors (LDLRs). Therefore, a greater LDL-C response to statins would be expected in individuals with PCSK9 loss-of-function (LOF) variants because LDLR degradation is reduced. To examine this hypothesis, the effect of 11 PCSK9 functional variants on statin response was determined in 669 African Americans. One LOF variant, rs11591147 (p.R46L) was significantly associated with LDL-C response to statin (P=0.002). In the three carriers, there was a 55.6% greater LDL-C reduction compared with non-carriers. Another functional variant, rs28362261 (p.N425S), was marginally associated with statin response (P=0.0064).The effect of rs11591147 was present in individuals of European ancestry (N=2388, P=0.054). The therapeutic effect of statins may be modified by genetic variation in PCSK9.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Inibidores de Hidroximetilglutaril-CoA Redutases
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Polimorfismo de Nucleotídeo Único
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Dislipidemias
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Pró-Proteína Convertase 9
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Variantes Farmacogenômicos
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LDL-Colesterol
Tipo de estudo:
Etiology_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Adult
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Aged
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Female
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Humans
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Male
/
Middle aged
Idioma:
En
Revista:
Pharmacogenomics J
Assunto da revista:
BIOLOGIA MOLECULAR
/
FARMACOLOGIA
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Estados Unidos