lipoprotein metabolism may be responsible for these
differences. Therefore typical healthy diet recommen-
dations may actually harm people who have a specific
genotype.
In women who have a particular SNP in the gene
encoding apolipoproteinA-1 (APOA1), an enzyme
involved in lipid metabolism, high levels of HDL cho-
lesterol are correlated with high consumption of poly-
unsaturated fatty acids (PUFA). In contrast women
who have the more common form of APOA1 have low
levels of HDL cholesterol with high consumption of
PUFA. Thus this SNP may be associated with a large
change in the risk for CVD. The relationship between
HDL cholesterol and PUFA is not seen in men. Thus
increased PUFA consumption—from foods such as
fish, vegetable oils, and nuts—would be expected to
benefit one group of women, harm another group of
women, and have little effect on men, although this
has not yet been scientifically demonstrated.
Similarly people carrying a particular SNP in the
gene encoding hepatic lipase respond to high-fat diets
with increased HDL cholesterol. People with varia-
tions in a gene called APOE, which is involved in
cholesterol balance, respond differently to low-fat
diets. One variant of the APOE gene is associated
with an increased risk for Alzheimer’s disease, but
only in Caucasians and Japanese. Black Africans
with the same variant do not have an increased risk.
Alterations in gene expression
SNPs can cause changes in gene-food interactions
by changing the way a protein encoded by the SNP-
containing gene interacts with a metabolite. SNPs can
also change the expression of a gene, causing the gene
to produce more or less protein. Chemicals in foods
can also directly or indirectly affect the expression of a
gene. Plant chemicals calledphytonutrientscan alter
the cell-signaling pathways that regulate gene expres-
sion. Small plant proteins called peptides can also alter
the regulation of gene expression. Lunasin is a sub-
stance insoythat has been associated with reduced
risks for heart disease and several cancers including
prostate cancer. Lunasin appears to increase the
expression of genes that monitor damage to DNA
and suppress the proliferation of tumor cells.
Nutritional factors can act as signaling molecules
that interact with a complex system of more than 540
enzymes called kinases. Kinases transmit signals from
the environment, including food, to the genome, turn-
ing on and off the expression of genes that produce the
proteins involved in metabolism. Two kinase path-
ways are known to be involved in:
satiety
insulin signaling
muscle energy reserves
lipid metabolism
inflammation.
These processes are associated withobesity, type 2
diabetes, and atherosclerosis. There are specific phy-
tonutrients that are known to affect these two kinase
pathways.
Epigenetic modifications are changes in gene
expression that do not affect the DNA sequence of
the gene. One of these modifications is DNA methyl-
ation, which attaches small molecules to the DNA.
During early development DNA methylation is highly
susceptible to nutritional and other environmental
influences.
Dietary components such as retinoic acid andzinc
can bind to DNA and affect gene expression. Zinc,
which is abundant in red meat and some seafoods,
turns on some genes and turns off others. For example
zinc activates genes associated with the production of
white blood cells that fight infection. Dietary fatty
acids can also directly modify gene expression.Commercial nutrigenomics
A number of companies offer genetic profiling or
genotyping of DNA that is obtained from a swab of
the inside of the cheek. The DNA analysis, along with
a detailed nutritional and lifestyle questionnaire, is
used to recommend individualized nutritional changes
for improving health and preventing disease. However
as of 2007 less than 20 genes were being tested for
variations that have nutrigenomic implications.
These include:
MTHFR
genes affecting cholesterol levels
genes affecting insulin sensitivity
a specific genetic variation that makes it more diffi-
cult to absorb calcium in the presence of caffeine.
The report, which costs $250–$1,500, may include
an estimate offolatelevels in the body based on the
questionnaire. Some companies then sell the client
supplements or products that are claimed to be
nutrigenomic.
For the majority of people a nutrigenomic diet
will not differ significantly from a standard diet that
includes plenty of fruits and vegetables. The client may
be told to get more exercise and to avoid:
alcohol
processed breadNutrigenomics