Nutrigenomics, Lipid Metabolism and Cardiovascular Disease
Jose M. Ordovas
Nutrition and Genomics Laboratory. JM-USDA-HNRCA at Tufts Univ., Boston, USA
Nutrigenomics is an emerging and promising multidisciplinary field that
focuses on studying the interactions between nutritional, genetic
factors, and health outcomes, using the new technical and conceptual
developments derived, in part, from the human genome project. The
ultimate goal of nutrigenomics is to elaborate more efficient
individual dietary intervention strategies aimed to preventing disease
and improving health status. To date, gene-diet interactions have been
carried out using the "candidate gene" approach. Our studies using the
Framingham Heart study as well as other population and intervention
studies have found already significant evidence for interactions
between dietary factors, genetic variants and biochemical markers of
cardiovascular disease. The traditional approach of recommending low
fat, low cholesterol diets for the entire population has been the
subject of heated discussion, based on the fact that some populations
with relatively high intakes of non-saturated fats have very low rates
of cardiovascular diseases and other chronic disorders. Now, we can
begin to characterize individuals that may respond better to one type
of recommendation or another. Therefore, a low fat, low cholesterol
strategy may be especially beneficial in terms of lowering plasma
cholesterol levels to those subjects carrying the apoE4 allele at the
APOE gene. The levels of HDL are modulated also by dietary, behavioral
and genetic factors. We have recently reported that the effect of
dietary PUFA intake on HDL-cholesterol concentrations is modulated by a
common genetic polymorphism in the promoter region of the APOA1 gene.
Thus, subjects carrying the A allele at the -75 G/A polymorphism show
an increase on HDL-C concentrations with increased intakes of PUFA;
whereas those homozygotes for the more common G allele have the
expected lowering on HDL-C levels as the intake of PUFA goes up. We
have also found significant interactions between intake of fat and
variability at the hepatic lipase locus that could also shed some light
to the different ability of certain ethnic groups to adapt to new
nutritional environments. At this regard we are carrying gene-diet
interactions studies in Singapore, a country inhabited by three ethnic
groups (Chinese, Indians and Malays). Our data is being contrasted with
those obtained in Framingham in order to gain more understanding about
potential gene-diet-ethnicity interactions. This knowledge could pave
the way for most successful dietary recommendations based on genetic
factors that may help to reduce cardiovascular risk more efficiently
than the current universal recommendations.
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