Diet-gene interactions in human lipoprotein metabolism.

Abstract

Genetic variation can influence the effects of hypocholesterolemic dietary interventions on lipoproteins involved in coronary artery disease (CAD). Individuals with the E4 allelic variant of the apo E gene exhibit greater low-density lipoprotein (LDL) cholesterol reductions on low-fat, low-cholesterol diets than subjects with other alleles. Another apolipoprotein structural variant, apo A-IV-2, attenuates the response of LDL cholesterol to dietary cholesterol. Other studies have associated lipoprotein response to dietary modifications with DNA polymorphisms in the genes for apo B and the LDL receptor, and in the promoter region of the apo A-I gene. Studies in our laboratory involving variation in dietary fat and carbohydrate intake have demonstrated that alleles at the apo E gene locus are associated with changes in large, buoyant but not smaller, denser LDL subclasses. On the other hand, a low-fat diet induces a reduction in small, dense LDL in individuals with a genetically influenced metabolic profile characterized by a predominance of these particles. Moreover, reductions in LDL cholesterol and apo B in these subjects are greater than in the majority of subjects with larger LDL. Since in humans a predominance of small LDL signifies a higher risk for coronary artery disease than that associated with larger LDL, metabolic and genetic factors contributing to the small LDL trait may account for a substantial portion of the coronary risk benefit attributed to reduced-fat diets. Studies in large population groups or in suitable animal models will be necessary to determine the impact of genetic influences on dietary response affecting lipoprotein metabolism and their interactions with other environmental and hormonal factors.

Genetic Variation at the ApoA-IV Gene Locus and Response to Diet in Familial Hypercholesterolemia

“…[23][24][25] The range of the response to changes in the amount or type of dietary fat and cholesterol varies among individuals. [35][36][37] As a group, our FH subjects (Table 2) responded to the NCEP-I diet with 15% and 17% reductions in total cholesterol and LDL-C, respectively, in agreement with what has been previously reported.…”

“…22 Changes in plasma lipid levels in response to dietary modifications vary greatly among individuals in the general population and are, in part, genetically controlled. [23][24][25] The response to diet in subjects with familial hypercholesterolemia (FH) is also highly variable 26 ; however, no studies have been performed on the influence of apoA-IV mutations on dietary response in these subjects. Our aim in this study was to investigate the effect of the genetic variants of apoA-IV at the 360 and 347 positions on the response to a hypolipidemic diet in a group of heterozygous subjects with FH.…”

Managing Abnormal Blood Lipids

“…Although there is considerable interindividual variation in response to these dietary interventions, [57][58][59] the reductions in LDL-C that may be expected with the adoption of diets that are low in saturated fat are Ϸ8% to 10% 5,60 and an additional 3% to 5% when dietary cholesterol is reduced (Ͻ200 mg/day). 5 Thus, implementation of a diet low in saturated fat and cholesterol would be expected to lower LDL-C by Ϸ11% to 15% 5 and possibly by as much as 20%.…”

AHA Dietary Guidelines

“…In recent years, there has been emerging evidence that this genetic variation can result in differing biological responses to specific nutrients and hence in differing optimum requirements for these nutrients among individuals. Genetic influences have been identified for plasma lipoprotein responses [201][202][203][204][205] to dietary fatty acids, cholesterol, and fiber; blood pressure responses to sodium; and homocysteine responses to folic acid. In addition, there is increasing evidence, mainly from animal models, for the roles of specific genes in influencing susceptibility to diet-induced obesity.…”