| Genotype influences plasma concentrations of nutrients
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| An example of the effect of genotype on nutrient intake is the response of plasma cholesterol concentration to its dietary content. Approximately 50% of individual variation in plasma cholesterol is genetically determined. Response to cholesterol-containing diet is associated with apoprotein E (apoE) genotype. ApoE is a protein synthesized in the liver, and is the main metabolic driver of the remnant particles (Chapter 17). It occurs in several isoforms coded by alleles designated e2, e3 and e4. It has been demonstrated that plasma cholesterol concentration increases on low fat/high cholesterol diet in persons with E4/4 but not E2/2, phenotype.
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| There are many examples of nutrients affecting gene expression. For instance, the activities of key hepatic enzymes differ in persons on a long-term high-fat diet compared to a high-carbohydrate diet (see Table 20.2). The amount of dietary cholesterol affects the activity of HMG-CoA reductase. Polyunsaturated fatty acids inhibit the expression of fatty acid synthase and the ω-3 fatty acids (see below) reduce the synthesis of RNA for the platelet-derived growth factor (PDGF) and inflammatory cytokine interleukin 1 (IL-1; Chapter 41). Another example comes from the field of hypertension: thirty to sixty percent of blood pressure variation is genotype-related and only 50% of patients with essential hypertension are salt-sensitive. The sensitivity to dietary salt is controlled, at least to an extent, by the angiotensinogen gene variants. Genetic factors are also fundamental in obesity: more than 50% of variation in weight is associated with the genetic background. Obesity is concordant in 74% between monozygotic- and 32% between dizygotic twins.
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