Apolipoprotein E gene promoter −219G→T polymorphism increases LDL-cholesterol concentrations and susceptibility to oxidation in response to a diet rich in saturated fat

Lipids and Atherosclerosis Research Unit, Reina Sofía University Hospital, Córdoba, Spain.
American Journal of Clinical Nutrition (Impact Factor: 6.77). 11/2004; 80(5):1404-9.
Source: PubMed


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.
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.
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.
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.
The -219G-->T polymorphism may partially explain differences in individual responses to diet.

Full-text preview

Available from:

  • No preview · Article · Apr 2005 · Chinese medical journal
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Cardiovascular diseases (CVD) result from complex interactions between genetic and environmental factors. The evidence supports that gene-environment interactions modulate plasma lipid concentrations and potentially CVD risk. The findings from studies examining gene-diet interactions and lipid metabolism have been promising. Several loci (eg, APOA1, APOE, LIPC) are providing proof of concept for the application of genetics in the context of personalized nutrition for CVD prevention. The spectrum of candidate genes has been expanding to incorporate those involved in intracellular lipid metabolism (eg, iPPARs, CYP7A1). However, the practical application of these findings is not ready for prime time. There is a compelling need for replication using a higher level of scientific evidence. Moreover, we need to evolve from the simple scenarios examined nowadays (ie, one single dietary component, SNP, and risk factor) to more realistic situations involving multiple interactions. In summary, there is need for both large population studies and well-standardized intervention studies.
    Full-text · Article · Dec 2005 · Current Cardiology Reports
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Insulin sensitivity (IS) is determined by genetic and environmental factors, including diet. The apoE gene promoter -219G/T polymorphism is associated with coronary heart disease and increased postprandial triacylglycerol-rich lipoprotein concentration, circumstances related to insulin resistance. Thus, our aim was to determine whether this polymorphism modified the IS response to dietary fat in healthy young adults. Volunteers (n = 43) with the apoE3/E3 genotype (8 GG, 25 GT and 10 TT) completed 3 dietary periods, each lasting 4 wk. They first consumed a SFA-rich diet [38% fat (% of energy in the total diet), 20% SFA (% of energy in the total diet)], and then, in a randomized, crossover design, a carbohydrate (CHO)-rich diet (30% fat, 55% CHO) or a monounsaturated fatty acid (MUFA)-rich diet (38% fat, 22% MUFA). After each diet period, we investigated peripheral IS using the insulin suppression test. The steady-state plasma glucose (SSPG) concentration was lower (P < 0.05) in GG subjects than in GT and TT individuals, regardless of the diet consumed. Significant diet x genotype interactions were found for SSPG and plasma nonesterified FFA (NEFA) concentrations. Thus, the shift from the SFA-rich diet to the MUFA- or CHO-rich diets decreased (P < 0.05) the SSPG and NEFA concentrations in GG and GT, but not in TT subjects. In conclusion, carriers of the -219T allele are less insulin sensitive than GG individuals. Furthermore, only carriers of the -219G allele have improved IS when MUFA- or CHO-rich diets are consumed instead of a SFA-rich diet.
    Full-text · Article · Dec 2005 · Journal of Nutrition
Show more