Apolipoprotein E mRNA expression in mononuclear cells from normolipidemic and hypercholesterolemic individuals treated with atorvastatin

作者：Cerda Alvaro^*; Genvigir Fabiana D V; Willrich Maria A V; Arazi Simone S; Bernik Marcia M S; Dorea Egidio L; Bertolami Marcelo C; Faludi Andre A; Hirata Mario H; Hirata Rosario D C

来源：Lipids in Health and Disease, 2011, 10: 206.

DOI：10.1186/1476-511X-10-206

• apolipoproteina E
• hypercholesterolemia
• single nucleotide polymorphism (SNP)
• APOE gene expression
• atorvastatin

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 epsilon 2/epsilon 3/epsilon 4 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 epsilon 2/epsilon 3/epsilon 4 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 epsilon 2 allele have reduced risk for hypercholesterolemia (OR: 0.27, 95% I. C.: 0.08-0.85, p < 0.05) and NL epsilon 2 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 epsilon 2 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.

• 出版日期2011-11-10