title: Apolipoprotein E mRNA expression in mononuclear cells from normolipidemic and hypercholesterolemic individuals treated with atorvastatin.
abstract: BACKGROUND
  Apolipoprotein E (apoE) is a key component of the lipid metabolism. Polymorphisms at the apoE gene (APOE) have been associated with cardiovascular disease, lipid levels and lipid-lowering response to statins. We evaluated the effects on APOE expression of hypercholesterolemia, APOE ε2/ε3/ε4 genotypes and atorvastatin treatment in Brazilian individuals. The relationship of APOE genotypes and plasma lipids and atorvastatin response was also tested in this population.
  
  
  METHODS
  APOE ε2/ε3/ε4 and plasma lipids were evaluated in 181 normolipidemic (NL) and 181 hypercholesterolemic (HC) subjects. HC individuals with indication for lowering-cholesterol treatment (n = 141) were treated with atorvastatin (10 mg/day/4-weeks). APOE genotypes and APOE mRNA in peripheral blood mononuclear cells (PBMC) were analyzed by TaqMan real time PCR.
  
  
  RESULTS
  HC had lower APOE expression than NL group (p < 0.05) and individuals with low APOE expression showed higher plasma total and LDL cholesterol and apoB, as well as higher apoAI (p < 0.05). Individuals carrying ε2 allele have reduced risk for hypercholesterolemia (OR: 0.27, 95% I.C.: 0.08-0.85, p < 0.05) and NL ε2 carriers had lower total and LDL cholesterol and apoB levels, and higher HDL cholesterol than non-carriers (p < 0.05). APOE genotypes did not affect APOE expression and atorvastatin response. Atorvastatin treatment do not modify APOE expression, however those individuals without LDL cholesterol goal achievement after atorvastatin treatment according to the IV Brazilian Guidelines for Dyslipidemia and Atherosclerosis Prevention had lower APOE expression than patients with desirable response after the treatment (p < 0.05).
  
  
  CONCLUSIONS
  APOE expression in PBMC is modulated by hypercholesterolemia and the APOE mRNA level regulates the plasma lipid profile. Moreover the expression profile is not modulated neither by atorvastatin nor APOE genotypes. In our population, APOE ε2 allele confers protection against hypercholesterolemia and a less atherogenic lipid profile. Moreover, low APOE expression after treatment of patients with poor response suggests a possible role of APOE level in atorvastatin response.
authors.affiliation: Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of Sao Paulo, Brazil. alvarocerda@usp.br
authors.forename: Alvaro
authors.initials: A
authors.lastname: Cerda
authors.forename: Fabiana D V
authors.initials: FD
authors.lastname: Genvigir
authors.forename: Maria A V
authors.initials: MA
authors.lastname: Willrich
authors.forename: Simone S
authors.initials: SS
authors.lastname: Arazi
authors.forename: Marcia M S
authors.initials: MM
authors.lastname: Bernik
authors.forename: Egidio L
authors.initials: EL
authors.lastname: Dorea
authors.forename: Marcelo C
authors.initials: MC
authors.lastname: Bertolami
authors.forename: Andre A
authors.initials: AA
authors.lastname: Faludi
authors.forename: Mario H
authors.initials: MH
authors.lastname: Hirata
authors.forename: Rosario D C
authors.initials: RD
authors.lastname: Hirata
mesh_terms: D000328:Adult; D000368:Aged; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D001057:Apolipoproteins E / Q000235:genetics* / Q000378:metabolism; D000069059:Atorvastatin; D016022:Case-Control Studies; D005260:Female; D015870:Gene Expression; D056726:Genetic Association Studies; D005838:Genotype; D006538:Heptanoic Acids / Q000627:therapeutic use*; D006801:Humans; D006937:Hypercholesterolemia / Q000188:drug therapy*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism*; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011758:Pyrroles / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism
chemical_list: D000924:Anticholesteremic Agents; D001057:Apolipoproteins E; D006538:Heptanoic Acids; D008055:Lipids; D011758:Pyrroles; D012333:RNA, Messenger; D000069059:Atorvastatin
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