Genetic differences exist between individuals. We are all roughly the same internally, as we belong to the same species, Homo sapiens. However, within the normal human type small genetic variations alter the way that we respond to our environments. There are many known examples of genetic differences (polymorphisms) that cause a varying response to foods, and this is the basis for the recommendation that each person should find a diet that is right for their unique biochemical individuality. Most physiological parameters exist along a range of values, with a normal distribution of responses applying along that range. Insulin sensitivity for example is vastly different between individuals even prior to the influence of outside factors that can modify the responses further. The normal fasting levels of triglycerides also vary between individuals and this is thought to result from polymorphisms in multiple genes, including the presence of the Apolipoprotein E (APOE) genotype.
The Apolipoprotein E genotype is a well studied polymorphism, and this research was initiated because of observations that particular isoforms of the genotype increased the risk of cardiovascular disease significantly. The Apolipoprotein E genotype exists as E2, E3 or E4 variants, with each individual possessing two copies of a combination of these variants. So individuals for example can have E2/E3, E3/E3 or E4/E2 variants as their genotype. Evidence suggests that those that possess one or two copies of the apolipoprotein E4 variant may be at higher risk of cardiovascular disease. Individuals with the E4 isoform of the Apolipoprotein E have elevated levels of triglycerides and low density lipoprotein (LDL) in their plasma, suggesting a reduced clearance of lipids from the plasma. In contrast, those with two copies of the E2 variant may be at reduced risk of cardiovascular disease because they have naturally lower levels of both triglycerides and LDL cholesterol.
In a recent study1, researchers investigated the effects of a high fat meal on the plasma lipid responses of subjects with either E3/E3 or E3/E4 variants of the apolipoprotein gene. In all subjects, irrespective of the genotype, there was a longer delay between consumption of the meal and peak plasma triglycerides in the saturated compared to unsaturated fat meals. In subjects with the E4 variant, plasma concentrations of triglycerides were significantly lower following an unsaturated compared to saturated fat meal. These results support other data to show that significant differences in the response to food exists between individuals due to genetic differences. In this case the Apolipoprotein E4 polymorphism increased the plasma levels of triglycerides in response to a high saturated fat meal. However, the elevation was small and could be considered modest. Whether this elevation could contribute to any disease process is controversial, and in the context of other more important factors is likely inconsequential.
Dr Robert Barrington’s comments: While the Apolipoprotein E4 polymorphism may increase the risk of cardiovascular disease, it should not be concluded that this is due to the higher plasma levels of triglycerides and other lipids. This particular polymorphism may for example have other effects that are the cause of the increased risk. For example, in this study, the authors also observed high blood glucose levels in the Apolipoprotein E4 carrying subjects following the high fat meal, compared to the E3 carrying individuals. Genetic variation while important should also not be considered a death sentence. Epigenetics show that the traditional model of gene to protein information flow is flawed, and the information is indeed able to flow in the other direction. Environmental factors such as the foods we eat can affect our genes, and a healthy high quality diet, individually tailored to the person’s own needs can overcome many of the detrimental effects of polymorphisms in genes.
RdB
