Atorvastatin effects on SREBF1a and SCAP gene expression in mononuclear cells and its relation with lowering-lipids response.
BACKGROUND
The transcription factors SREBP1 and SCAP are involved in intracellular cholesterol homeostasis. Polymorphisms of these genes have been associated with variations on serum lipid levels and response to statins that are potent cholesterol-lowering drugs. We evaluated the effects of atorvastatin on SREBF1a and SCAP mRNA expression in peripheral blood mononuclear cells (PBMC) and a possible association with gene polymorphisms and lowering-cholesterol response.


METHODS
Fifty-nine hypercholesterolemic patients were treated with atorvastatin (10 mg/day for 4 weeks). Serum lipid profile and mRNA expression in PBMC were assessed before and after the treatment. Gene expression was quantified by real-time PCR using GAPD as endogenous reference and mRNA expression in HepG2 cells as calibrator. SREBF1 -36delG and SCAP A2386G polymorphisms were detected by PCR-RFLP.


RESULTS
Our results showed that transcription of SREBF1a and SCAP was coordinately regulated by atorvastatin (r=0.595, p<0.001), and that reduction in SCAP transcription was associated with the 2386AA genotype (p=0.019). Individuals who responded to atorvastatin with a downregulation of SCAP had also a lower triglyceride compared to those who responded to atorvastatin with an upregulation of SCAP.


CONCLUSIONS
Atorvastatin has differential effects on SREBF1a and SCAP mRNA expression in PBMC that are associated with baseline transcription levels, triglycerides response to atorvastatin and SCAP A2386G polymorphism.
Arazi
Simone Sorkin
SS
School of Pharmaceutical Sciences - University of Sao Paulo, Sao Paulo, SP, Brazil. sisorkin@usp.br
Genvigir
Fabiana Dalla Vecchia
FD
Willrich
Maria Alice Vieira
MA
Hirata
Mario Hiroyuki
MH
Dorea
Egidio Lima
EL
Bernik
Marcia
M
Hirata
Rosario Dominguez Crespo
RD
D000328:Adult; D000368:Aged; D000924:Anticholesteremic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D000069059:Atorvastatin; D001483:Base Sequence; D017931:DNA Primers; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D006538:Heptanoic Acids / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D006937:Hypercholesterolemia / Q000188:drug therapy*; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008055:Lipids / Q000097:blood; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011758:Pyrroles / Q000494:pharmacology* / Q000627:therapeutic use; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics*
D000924:Anticholesteremic Agents; D017931:DNA Primers; D006538:Heptanoic Acids; D047908:Intracellular Signaling Peptides and Proteins; D008055:Lipids; D008565:Membrane Proteins; D011758:Pyrroles; C497387:SREBF1 protein, human; C102196:SREBP cleavage-activating protein; D051780:Sterol Regulatory Element Binding Protein 1; D000069059:Atorvastatin