Effects of atorvastatin on CYP3A4 and CYP3A5 mRNA expression in mononuclear cells and CYP3A activity in hypercholeresterolemic patients.
Clin Chim Acta
; 421: 157-63, 2013 Jun 05.
Article
em En
| MEDLINE
| ID: mdl-23501331
ABSTRACT
BACKGROUND:
Variability of response to statins has been related to polymorphisms in genes involved in cholesterol homeostasis and statin metabolism, such as CYP3A4 and CYP3A5. We investigated the effects of atorvastatin on CYP3A4 and CYP3A5 mRNA expression in mononuclear cells and on CYP3A activity and their interactions with common variants.METHODS:
Unrelated individuals (n=121) with hypercholesterolemia (HC) were treated with atorvastatin (10 mg/day/4 weeks). Ninety-two normolipidemic (NL) subjects were selected as a control group. Genotype analysis of CYP3A4*1B (rs2740574), CYP3A4*22 (rs35599367), CYP3A5*3C (rs776746), and CYP3A5*1D (rs15524) and mRNA levels in peripheral blood mononuclear cells (PBMCs) were estimated. CYP3A activity was phenotyped by the urinary cortisol to 6-beta-hydroxy-cortisol ratio.RESULTS:
LDL cholesterol reduction in response to atorvastatin was positively correlated with change in CYP3A4 (R(2)=0.039, p=0.037) and CYP3A5 (R(2)=0.047, p=0.019) mRNA levels and negatively correlated with CYP3A activity (R(2)=0.071, p=0.022). CYP3A5*3C (AGT haplotype) was associated to lower basal CYP3A5 mRNA expression in HC (p<0.045), however none of the haplotype groups impacted treatment.CONCLUSION:
It is likely that cholesterolemia status changes promoted by atorvastatin play a role in regulating CYP3A4 and CYP3A5 mRNA expression in PBMCs, as well as CYP3A activity. CYP3A5*3C (AGT haplotype) also contributes for the variability of CYP3A5 mRNA levels in PBMCs.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Pirróis
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Leucócitos Mononucleares
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Expressão Gênica
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Citocromo P-450 CYP3A
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Ácidos Heptanoicos
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Hipercolesterolemia
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Anticolesterolemiantes
Tipo de estudo:
Observational_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
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Middle aged
Idioma:
En
Revista:
Clin Chim Acta
Ano de publicação:
2013
Tipo de documento:
Article