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Nutrient-Gene Interactions

The Apolipoprotein E Gene Promoter (–219G/T) Polymorphism Determines Insulin Sensitivity in Response to Dietary Fat in Healthy Young Adults¹

Lipids and Atherosclerosis Research Unit, Hospital Universitario Reina Sofía, Córdoba, Spain and ^* UMR 476-INSERM/1260-INRA, University and Central Analytical Laboratory, Ste Marguerite University Hospital, Marseille, France

²To whom correspondence should be addressed. E-mail: md1lomij{at}uco.es.

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.

KEY WORDS: • apoE gene promoter (–219G/T) polymorphism • dietary intervention • insulin sensitivity • genetics

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