title: Apolipoprotein E gene promoter -219G->T polymorphism increases LDL-cholesterol concentrations and susceptibility to oxidation in response to a diet rich in saturated fat.
abstract: BACKGROUND
  The apolipoprotein E (APOE) gene promoter polymorphism (-219G-->T) has been associated with increased risk of myocardial infarction, premature coronary artery disease, and decreased plasma apolipoprotein E concentrations.
  
  
  OBJECTIVE
  We aimed to determine in healthy subjects whether this polymorphism modifies the susceptibility of LDL to oxidation and the lipid response to the content and quality of dietary fat.
  
  
  METHODS
  Fifty-five healthy men with the APOE3/E3 genotype (7 GG, 38 GT, and 10 TT) completed 3 dietary periods, each lasting 4 wk. The first was a saturated fatty acid (SFA)-rich diet [38% fat-20% SFA and 12% monounsaturated fatty acid (MUFA)-and 47% carbohydrates (CHO)], which was followed by a CHO-rich diet (30% fat-<10% SFA and 12% MUFA-and 55% CHO) or a MUFA-rich diet (38% fat-<10% SFA and 22% MUFA-and 47% CHO) in a randomized crossover design. At the end of each dietary period, LDL oxidation susceptibility, lipids, and lipoproteins were measured.
  
  
  RESULTS
  Compared with carriers of the G allele, TT subjects had a significantly (P < 0.05) shorter lag time after the SFA diet. The replacement of the SFA diet by the CHO or MUFA diet induced a greater increase (P < 0.05) in lag time in the TT subjects than in the GG or GT subjects. Carriers of the T allele had higher LDL-cholesterol (P < 0.05) and apolipoprotein B (P < 0.05) plasma concentrations after the SFA diet than did GG subjects. Compared with GG subjects, carriers of the T allele had a significantly (P < 0.05) greater decrease in LDL cholesterol and apolipoprotein B when they changed from the SFA to the CHO diet.
  
  
  CONCLUSIONS
  The -219G-->T polymorphism may partially explain differences in individual responses to diet.
authors.affiliation: Lipids and Atherosclerosis Research Unit, Reina Sofía University Hospital, Córdoba, Spain.
authors.forename: Juan Antonio
authors.initials: JA
authors.lastname: Moreno
authors.forename: Francisco
authors.initials: F
authors.lastname: Pérez-Jiménez
authors.forename: Carmen
authors.initials: C
authors.lastname: Marín
authors.forename: Purificación
authors.initials: P
authors.lastname: Gómez
authors.forename: Pablo
authors.initials: P
authors.lastname: Pérez-Martínez
authors.forename: Rafael
authors.initials: R
authors.lastname: Moreno
authors.forename: Cecilia
authors.initials: C
authors.lastname: Bellido
authors.forename: Francisco
authors.initials: F
authors.lastname: Fuentes
authors.forename: José
authors.initials: J
authors.lastname: López-Miranda
mesh_terms: D053318:Apolipoprotein E3; D001057:Apolipoproteins E / Q000187:drug effects / Q000235:genetics*; D002318:Cardiovascular Diseases / Q000209:etiology; D008078:Cholesterol, LDL / Q000097:blood* / Q000187:drug effects; D004041:Dietary Fats / Q000494:pharmacology*; D005227:Fatty Acids / Q000008:administration & dosage / Q000494:pharmacology*; D005838:Genotype; D006801:Humans; D008297:Male; D010084:Oxidation-Reduction / Q000187:drug effects; D011110:Polymorphism, Genetic / Q000187:drug effects*; D012306:Risk
chemical_list: D053318:Apolipoprotein E3; D001057:Apolipoproteins E; D008078:Cholesterol, LDL; D004041:Dietary Fats; D005227:Fatty Acids