title: Influence of polymorphisms and cholesterol-lowering treatment on SCARB1 mRNA expression.
abstract: OBJECTIVE
  This study evaluated the influence of polymorphisms and cholesterol-lowering treatments on SCARB1 mRNA expression in peripheral blood mononuclear cells and in HepG2 and Caco-2 cells.
  
  
  METHODS
  Blood samples were drawn from normolipidemic (NL, n = 166) and hypercholesterolemic (HC, n = 123) individuals to extract DNA and total RNA and to analyze the lipid profile. After a 4-week washout period, 98 HC individuals were treated with atorvastatin (10 mg/day/4 weeks) whereas 25 were treated with ezetimibe (10 mg/day/4 weeks), followed by simvastatin (10 mg/day/8 weeks) and simvastatin plus ezetimibe (10 mg each/day/4 weeks). HepG2 and Caco-2 cells were treated with atorvastatin, simvastatin and ezetimibe at various concentrations for 12 and 24 h and collected for RNA extraction. SCARB1 mRNA expression was measured by TaqMan® assay and SCARB1 c.4G> A, c.726 + 54C> T and c.1080C> T polymorphisms were detected by PCR-RFLP.
  
  
  RESULTS
  High LDL cholesterol (> 160 mg/dL) values were associated with low baseline SCARB1 mRNA expression in PBMC. Allele T carriers for SCARB1 c.726+54C> T had lower basal SCARB1 transcription in PBMC (p < 0.05). Simvastatin, atorvastatin and ezetimibe treatments did not modify the SCARB1 mRNA level in PBMC from HC patients. Similarly, these cholesterol-lowering drugs did not modulate the SCARB1 expression in HepG2 and Caco-2 cells in spite of the concentration and time of exposure (p > 0.05).
  
  
  CONCLUSIONS
  LDL cholesterol levels and SCARB1 c.726 + 54C> T are associated with low mRNA expression in mononuclear cells. Cholesterol-lowering drugs do not modulate SCARB1 expression in PBMC from HC subjects or in HepG2 and Caco-2 cells.
authors.affiliation: Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of Sao Paulo, Sao Paulo, Brazil. alvarocerda@usp.br
authors.forename: Álvaro
authors.initials: Á
authors.lastname: Cerda
authors.forename: Fabiana Dalla Vecchia
authors.initials: FD
authors.lastname: Genvigir
authors.forename: Alice Cristina
authors.initials: AC
authors.lastname: Rodrigues
authors.forename: Maria Alice Vieira
authors.initials: MA
authors.lastname: Willrich
authors.forename: Egidio Lima
authors.initials: EL
authors.lastname: Dorea
authors.forename: Márcia Martins Silveira
authors.initials: MM
authors.lastname: Bernik
authors.forename: Simone Sorkin
authors.initials: SS
authors.lastname: Arazi
authors.forename: Raquel de
authors.initials: Rd
authors.lastname: Oliveira
authors.forename: Mario Hiroyuki
authors.initials: MH
authors.lastname: Hirata
authors.forename: Rosario Dominguez Crespo
authors.initials: RD
authors.lastname: Hirata
mesh_terms: D000328:Adult; D000368:Aged; D000924:Anticholesteremic Agents / Q000008:administration & dosage; D000069059:Atorvastatin; D001384:Azetidines / Q000008:administration & dosage; D018938:Caco-2 Cells; D004247:DNA / Q000378:metabolism; D000069438:Ezetimibe; D005260:Female; D056945:Hep G2 Cells; D006538:Heptanoic Acids / Q000008:administration & dosage; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood; D007963:Leukocytes, Mononuclear / Q000166:cytology; D008055:Lipids / Q000737:chemistry; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011758:Pyrroles / Q000008:administration & dosage; D012333:RNA, Messenger / Q000378:metabolism; D051122:Scavenger Receptors, Class B / Q000235:genetics*; D019821:Simvastatin / Q000008:administration & dosage
chemical_list: D000924:Anticholesteremic Agents; D001384:Azetidines; D006538:Heptanoic Acids; D008055:Lipids; D011758:Pyrroles; D012333:RNA, Messenger; C495124:SCARB1 protein, human; D051122:Scavenger Receptors, Class B; D004247:DNA; D000069059:Atorvastatin; D019821:Simvastatin; D000069438:Ezetimibe