title: Pharmacogenetic study of apolipoprotein E, cholesteryl ester transfer protein and hepatic lipase genes and simvastatin therapy in Brazilian subjects.
abstract: BACKGROUND
  In recent years, one of the focuses of genetic investigation in cardiology has been to identify the genetic factors associated with variable response to statin treatment. Polymorphisms in apolipoprotein E (APOE), cholesteryl ester transfer protein (CETP) and hepatic lipase (LIPC), proteins with major roles in lipid metabolism and homeostasis have been shown associated with lipid-lowering drugs response.
  
  
  METHODS
  One hundred forty-six hypercholesterolemic patients of European descent were prospectively enrolled and treated with simvastatin 20 mg per day for over 6 months. Ninety-nine subjects completed the 6-month follow-up. Plasma lipids and lipoproteins were measured before and throughout the study. APOE (E*2, E*3 and E*4), LIPC-250A > G and CETP TaqIB genotypes were determined by PCR and restriction mapping.
  
  
  RESULTS
  After a 6-month follow-up, no differences among genotypes in the percentage variation in lipid and lipoprotein concentrations for APOE and LIPC SNPs were observed. After adjustment for covariates, CETP B2B2 homozygotes showed a greater HDL-cholesterol increase compared to B1B2 and B1B1 subjects (14.1% vs. 1.7% and 1.3%, P < 0.05, respectively).
  
  
  CONCLUSIONS
  Our study demonstrates that individual plasma HDL-cholesterol response to simvastatin is mediated, in part, by the CETP gene locus, with the B2 homozygotes having more benefit in HDL-C improvement than carriers of B1 allele.
authors.affiliation: Departamento de Genética, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: Marilu
authors.initials: M
authors.lastname: Fiegenbaum
authors.forename: Fabiano R
authors.initials: FR
authors.lastname: da Silveira
authors.forename: Cézar R
authors.initials: CR
authors.lastname: Van der Sand
authors.forename: Luiz Carlos
authors.initials: LC
authors.lastname: Van der Sand
authors.forename: Maria E W
authors.initials: ME
authors.lastname: Ferreira
authors.forename: Renan C
authors.initials: RC
authors.lastname: Pires
authors.forename: Mara H
authors.initials: MH
authors.lastname: Hutz
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001057:Apolipoproteins E / Q000235:genetics*; D001938:Brazil; D002352:Carrier Proteins / Q000235:genetics*; D053480:Cholesterol Ester Transfer Proteins; D005260:Female; D006023:Glycoproteins / Q000235:genetics*; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood / Q000188:drug therapy; D008049:Lipase / Q000235:genetics* / Q000378:metabolism; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D010597:Pharmacogenetics; D019821:Simvastatin / Q000627:therapeutic use*
chemical_list: D001057:Apolipoproteins E; C506642:CETP protein, human; D002352:Carrier Proteins; D053480:Cholesterol Ester Transfer Proteins; D006023:Glycoproteins; C504173:LIPC protein, human; D008055:Lipids; D019821:Simvastatin; D008049:Lipase