Apolipoprotein E gene promoter -219G->T polymorphism increases LDL-cholesterol concentrations and susceptibility to oxidation in response to a diet rich in saturated fat.
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.
Moreno
Juan Antonio
JA
Lipids and Atherosclerosis Research Unit, Reina Sofía University Hospital, Córdoba, Spain.
Pérez-Jiménez
Francisco
F
Marín
Carmen
C
Gómez
Purificación
P
Pérez-Martínez
Pablo
P
Moreno
Rafael
R
Bellido
Cecilia
C
Fuentes
Francisco
F
López-Miranda
José
J
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
D053318:Apolipoprotein E3; D001057:Apolipoproteins E; D008078:Cholesterol, LDL; D004041:Dietary Fats; D005227:Fatty Acids