Ancestry and other genetic associations with plasma PCSK9 response to simvastatin.
Pharmacogenet Genomics
; 24(10): 492-500, 2014 Oct.
Article
en En
| MEDLINE
| ID: mdl-25089948
ABSTRACT
OBJECTIVE:
Statins stimulate transcription of proprotein convertase subtilisin/kexin type 9 (PCSK9), a negative regulator of the low-density lipoprotein receptor, thus blunting the cholesterol-lowering effects of statin treatment. Although there is interindividual variation in PCSK9 statin response, little is known about ancestral and other genetic factors that could contribute to this variation.METHODS:
We measured plasma PCSK9 levels before and after 6 weeks of treatment with 40 mg/day simvastatin in 901 participants of the Cholesterol and Pharmacogenetics clinical trial and tested phenotypic and genetic factors for correlation with PCSK9 statin response.RESULTS:
Statin-induced changes in plasma low-density lipoprotein cholesterol, total cholesterol, and apolipoprotein B were all significantly correlated with statin-induced changes in PCSK9. A detailed examination of the associations of genetic ancestry with PCSK9 statin response revealed that Ashkenazi Jews had smaller statin-induced increases in PCSK9 levels than other self-reported Caucasians (P=0.016). Using genomewide association analysis, we found that the 'G' minor allele of rs13064411 in the WD repeat domain 52 (WDR52) gene was significantly associated with greater statin-induced increases in plasma PCSK9 in Caucasians (P=8.2 × 10(-8)) in the Cholesterol and Pharmacogenetics trial.CONCLUSION:
Overall, these results suggest that genetic ancestry and the rs13064411 genotype contribute to interindividual variation in PCSK9 statin response in Caucasians.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Proteínas Nucleares
/
Serina Endopeptidasas
/
Simvastatina
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Polimorfismo de Nucleótido Simple
/
Proproteína Convertasas
/
Grupos Raciales
/
Estudios de Asociación Genética
Tipo de estudio:
Prognostic_studies
/
Risk_factors_studies
Límite:
Female
/
Humans
/
Male
Idioma:
En
Revista:
Pharmacogenet Genomics
Asunto de la revista:
FARMACOLOGIA
/
GENETICA MEDICA
Año:
2014
Tipo del documento:
Article
País de afiliación:
Estados Unidos