Genetic variation in the ABCC2 gene is associated with dose decreases or switches to other cholesterol-lowering drugs during simvastatin and atorvastatin therapy.
Pharmacogenomics J
; 13(3): 251-6, 2013 Jun.
Article
em En
| MEDLINE
| ID: mdl-22186618
ABSTRACT
Several statins are substrates for the multidrug resistance-associated protein 2 transporter, encoded by the ABCC2 gene. We analyzed in the Rotterdam Study whether the common polymorphisms -24C>T, 1249G>A and 3972C>T in the ABCC2 gene were associated with a dose decrease or switch to another cholesterol-lowering drug in simvastatin and atorvastatin users. These events could indicate an adverse effect or a too strong reduction in cholesterol level. We identified 1014 simvastatin and atorvastatin users during the period 1 January 1991 to 1 January 2010. Associations between genetic variation and the risk of these events were analyzed using Cox proportional hazards modelling. The ABCC2 -24C>T genotype (HR 1.32 95% CI 1.04-1.69) and the H12 haplotype versus the H2 haplotype (HR 1.49; 95% CI 1.06-2.09) were associated with these events in simvastatin users. A similar but not significant association was found in atorvastatin users. To conclude, genetic variation in the ABCC2 gene is associated with these events in simvastatin users.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Pirróis
/
Sinvastatina
/
Proteínas Associadas à Resistência a Múltiplos Medicamentos
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Relação Dose-Resposta a Droga
/
Ácidos Heptanoicos
Tipo de estudo:
Risk_factors_studies
Limite:
Aged
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Female
/
Humans
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Male
/
Middle aged
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article