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ABCB1 and ABCC1 expression in peripheral mononuclear cells is influenced by gene polymorphisms and atorvastatin

Ivanise Marina Moretti Rebecchi1, Alice Cristina Rodrigues, Simone Sorkin Arazi

  • 1Faculty of Pharmaceutical Sciences, University of Sao Paulo, and University Hospital, Sao Paulo, Brazil. rebecchi@usp.br

Biochemical Pharmacology
|October 15, 2008
PubMed

Insights

Atorvastatin reduces ABCB1 and ABCC1 mRNA in peripheral blood mononuclear cells (PBMC). ABCB1 gene variants and baseline mRNA influence cholesterol-lowering response to atorvastatin.

Area of Science:

  • Pharmacogenomics
  • Molecular Biology
  • Cardiovascular Research

Background:

  • Statins, like atorvastatin, are widely used to manage hypercholesterolemia.
  • Genetic variations and gene expression levels can influence drug response.
  • ABCB1 and ABCC1 are important drug transporters potentially affecting statin efficacy.

Purpose of the Study:

  • To investigate the impact of atorvastatin on ABCB1 and ABCC1 mRNA expression in PBMCs.
  • To explore the relationship between these gene expressions, specific polymorphisms, and the cholesterol-lowering effects of atorvastatin.
  • To understand how ABCB1 polymorphisms relate to coronary artery disease (CAD) risk.

Main Methods:

  • Study included 136 hypercholesterolemic patients treated with atorvastatin (10 mg/day for 4 weeks).
  • Serum lipids and apolipoproteins were measured.
  • DNA and RNA were extracted from peripheral blood mononuclear cells (PBMCs).
  • ABCB1 (C3435T, G2677T/A) and ABCC1 (G2012T) polymorphisms were analyzed using PCR-RFLP.
  • ABCB1 and ABCC1 mRNA expression in PBMCs was quantified using real-time PCR.

Main Results:

  • Atorvastatin treatment led to a significant 50% reduction in both ABCB1 and ABCC1 mRNA expression in PBMCs (p<0.05).
  • Reduction in ABCB1 expression was linked to the ABCB1 G2677T/A polymorphism (p=0.039).
  • Lower baseline ABCB1 mRNA levels correlated with a reduced response in lowering LDL cholesterol and apolipoprotein B levels.

Conclusions:

  • Atorvastatin modulates ABCB1 and ABCC1 mRNA levels in PBMCs.
  • The ABCB1 G2677T/A polymorphism influences this modulation.
  • Baseline ABCB1 mRNA expression is a predictor of individual response to atorvastatin in terms of serum LDL cholesterol and apoB reduction.

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