ABCB1 and ABCC1 expression in peripheral mononuclear cells is influenced by gene polymorphisms and atorvastatin treatment
Biochemical Pharmacology
; 77: 66-75, 2009.
Article
in English
| Sec. Est. Saúde SP, SESSP-IDPCPROD, Sec. Est. Saúde SP
| ID: biblio-1060819
Responsible library:
BR79.1
Localization: BR79.1
ABSTRACT
This study investigated the effects of atorvastatin on ABCB1 and ABCC1 mRNA expression on peripheral blood mononuclear cells (PBMC) and their relationship with gene polymorphismsand lowering-cholesterol response. One hundred and thirty-six individuals withhypercholesterolemia were selected and treated with atorvastatin (10 mg/day/4 weeks). Blood samples were collected for serum lipids and apolipoproteins measurements and DNA and RNA extraction. ABCB1 (C3435T and G2677T/A) and ABCC1 (G2012T) gene polymorphisms were identified by polymerase chain reaction-restriction (PCR)-RFLP and mRNA expression was measured in peripheral blood mononuclear cells by singleplex real-time PCR. ABCB1 polymorphisms were associated with risk for coronary artery disease (CAD) ( p 0.085 LDL-c = 40.3 14.3%; apoB = 32.5 10.7%; p < 0.05). ABCB1 substrates or inhibitors did not affect the baseline expression, while ABCB1 inhibitors reversedthe effects of atorvastatin on both ABCB1 and ABCC1 transporters. In conclusion, ABCB1 and ABCC1 mRNA levels in PBMC are modulated by atorvastatin and ABCB1 G2677T/A polymorphism and ABCB1 baseline expression is related to differences in serum LDL cholesterol and apoB in response to atorvastatin.
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Collection:
National databases
/
Brazil
Database:
Sec. Est. Saúde SP
/
SESSP-IDPCPROD
Main subject:
Pharmacogenetics
/
Polymorphism, Genetic
/
Gene Expression
Language:
English
Journal:
Biochemical Pharmacology
Year:
2009
Document type:
Article
Institution/Affiliation country:
Faculty of Pharmaceutical Sciences, University of Sao Paulo/BR
/
Instituto Dante Pazzanese de Cardiologia/BR