Catalyzing Inquiry at the Interface of Computing and Biology

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322 CATALYZING INQUIRY

Science (NIGMS), PharmGKB is a publicly available, Internet-accessible database for pharmacogenetics
and pharmacogenomics. Its overall aim is to aid researchers in understanding how genetic variation
among individuals contributes to differences in reactions to drugs.^58 The database integrates pharma-
codynamics (drug actions), pharmacokinetics (drug metabolism), toxicity, sequence and other molecu-
lar data, pathway information, and patient data.


9.7.3 Nutritional Genomics
Traditional nutrition research has had among its goals the establishment of overarching dietary
recommendations for everyone—in principle, for the world’s entire population. Today, and more so in
the future, the implications of individual genetic makeup for optimal diet have changed that perspec-
tive. To understand and exploit the interplay of diet and genetics, nutritional genomics is a relatively
new specialization within the life sciences with two separate but related foci. One focus relates an
individual’s genetic makeup to dietary regimes that are more or less healthy for him or her. For ex-
ample, it is well known that some individuals are more likely to suffer from high blood pressure if they
consume salt in relatively large quantities, while others are not. Poch et al.^59 found a possible genetic
basis on which to differentiate salt-sensitive individuals and salt-insensitive ones. If it is possible to
develop genetic tests for salt sensitivity, salt-sensitive individuals could be advised specifically to limit
their salt intake, and salt-insensitive individuals could continue to indulge at will their taste for salty
snacks.
The traditional focus of nutrition research is not in any way rendered irrelevant by nutritional
genomics. Still, beyond general good advice and informed common sense, in the most ambitious sce-
narios, recommended dietary profiles could be customized for individuals based on their specific ge-
nomic composition. Ordovas and Corella write:^60


Nutritional genomics has tremendous potential to change the future of dietary guidelines and personal
recommendations. Nutrigenetics will provide the basis for personalized dietary recommendations based
on the individual’s genetic makeup. This approach has been used for decades for certain monogenic
diseases; however, the challenge is to implement a similar concept for common multifactorial disorders
and to develop tools to detect genetic predisposition and to prevent common disorders decades before
their manifestation.... [P]reliminary evidence strongly suggests that the concept should work and that
we will be able to harness the information contained in our genomes to achieve successful aging using
behavioral changes; nutrition will be the cornerstone of this endeavor.

A second focus of nutritional genomics is on exploiting the potential for modifying foodstuffs to be
more healthy, and so dietary advice and discipline might be supplanted in part by such modifications.
For example, it may be possible to redesign the lipid composition of oil seed crops using genetic
modification techniques (through either selective breeding or genetic engineering). However, whether
this is desirable depends on how consumption of a different mix of lipids affects human health. Watkins
et al.^61 argue for an understanding of the overall metabolomic expression of lipid metabolism to ensure
that a particular metabolite composition truly improves overall health, so that a change in lipid compo-
sition that is deemed healthy when viewed as lowering the risk of one disease does not simultaneously
increase the risk of developing another.


(^58) T.E. Klein and R.B. Altman, “PharmGKB: The Pharmacogenetics and Pharmacogenomics Knowledge Base,” Pharmacogenomics
Journal 4(1):1, February 2004.
(^59) E. Poch, D. Gonzalez, V. Giner, E. Bragulat, A. Coca, and A. de La Sierra, “Molecular Basis of Salt Sensitivity in Human
Hypertension: Evaluation of Renin-Angiotensin-Aldosterone System Gene Polymorphisms,” Hypertension 38(5):1204-1209, 2001.
(^60) J.M. Ordovas and D. Corella, “Nutritional Genomics,” Annual Review of Genomics and Human Genetics 5:71-118, 2004.
(^61) S.M. Watkins, B.D. Hammock, J.W. Newman, and J.B. German, “Individual Metabolism Should Guide Agriculture Toward
Foods for Improved Health and Nutrition,” American Journal of Clinical Nutrition 74(3):283-286, 2001.

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