Nutritional genomics
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/*See also*/ Roger Williams, PhD, discoverer of B5 & founder of the Biochemical Inst at UTexas, was a visionary in the understanding of biochemical uniqueness. book: Biochemical Individuality (1956)
'''Nutritional genomics''' is a science studying the relationship between human genome, nutrition and health.
It can be divided into two disciplines:
*[[Nutrigenomics]]: studies the effect of nutrients on health through altering [[genome]], [[proteome]], [[metabolome]] and the resulting changes in physiology.
*[[Nutrigenetics]]: studies the effect of genetic variations on the interaction between diet and health with implications to susceptible subgroups.
==Gene-Diet-Disease interaction==
97% of the genes known to be associated with human diseases result in ''monogenic diseases'', i.e. a mutation in one gene is sufficient to cause the disease. Modifying the dietary intake can prevent some monogenic diseases. One example is [[phenylketonuria]], a genetic disease characterized by a defective [[phenylalanine hydroxylase]] enzyme, which is normally responsible for the metabolism of [[phenylalanine]] to [[tyrosine]]. This results in the accumulation of phenylalanine and its breakdown products in the blood and the decrease in tyrosine, which increases the risk of neurological damage and mental retardation. Phenylalanine-restricted tyrosine-supplemented diets are a means to nutritionally treat this monogenic disease.
In contrast, diseases currently in the world, e.g. obesity, cancer, diabetes, and cardiovascular diseases, are ''polygenic diseases'', i.e. they arise from the dysfunction in a cascade of genes, and not from a single mutated gene. Dietary intervention to prevent the onset of such diseases is a complex and ambitious goal.
Recently, it was discovered that the health effects of food compounds are related mostly to specific interactions on molecular level, i.e. dietary constituents participate in the regulation of gene expression by modulating the activity of [[transcription factor]]s, or through the secretion of hormones that in turn interfere with a transcription factor.
==Nutrigenomics==
Nutrigenomics refers to the prospective analysis of differences among nutrients in the regulation of [[gene expression]] i.e., it studies the effect of nutrients on the genome, proteome, and metabolome.
It involves the application of high-throughput [[genomic]] tools such as [[DNA microarray]] technology in nutrition research. Nutrigenomics is a discovery science which aims at understanding how nutrition influences metabolic pathways and homeostatic control and how this regulation is disturbed in the early phase of a diet-related disease.
===Biomics technologies===
The recent advances in nutrigenomics studies are owed to the completion of [[human genome project]] and the new biomics technologies that provide means for the simultaneous determination of the expression of many thousands of genes at the [[mRNA]] ([[transcriptomics]]), metabolites ([[metabolomics]]) and protein ([[proteomics]]) levels.
Genomic and transcriptomic studies are mostly conducted by [[DNA microarray]] technologies. Proteomics and metabolomics have no standardized procedures yet, but usually, proteome analysis is done by [[two-dimensional gel electrophoresis]] and [[Liquid chromatography-mass spectrometry]], while metabolome analysis is conducted through [[gas chromatography-mass spectrometry]], [[liquid chromatography-mass spectrometry]] and [[liquid chromatography]]-[[nuclear magnetic resonance]].
Usually, these technologies are applied in a “differential display” mode, i.e. by comparing two situations (e.g. diseased versus healthy) in order to reduce the complexity in data by examining only differences.
===Example of applications===
An example of the application of the nutrigenomic approach was [http://www.sciencemag.org/cgi/content/abstract/sci;290/5497/1771 a study] that simultaneously identified a mechanism for the regulation of [[sterol]] uptake in the intestine and the basis for [[sitosterolemia]] (a genetic disorder characterized by hyperabsorption of dietary sterols leading to hypercholesterolemia with a high risk of developing atherosclerosis). In the study, a group of mice was treated with a [[lipid metabolism]]-altering drug and DNA microarray technology was used for mRNA [[expression profiling]] of various tissues. Differential display mode was used by comparing differences in expression levels with a control group of mice. This led to the discovery of an unknown gene. Through computer simulation techniques, it was found that two proteins produced by the newly discovered gene were responsible for the regulated reverse transport of animal and plant dietary sterols out of the apical surface of intestinal cells. By exploring human gene databases, a human homologue of the mouse gene was identified. This explained why dietary sterols, which are structurally similar to [[cholesterol]], are not absorbed in normal individuals. By scanning sitosterolemic individuals for this gene, it was found that all of them had a mutation in this gene responsible for their uncontrolled hyperabsorption of dietary sterols.
==Nutrigenetics==
Nutrigenetics is the retrospective analysis of genetic variations among individuals with respect to the interaction between diet and disease. It is an applied science that studies how the [[genotype|genetic makeup]] of an individual affects the response to diet and the susceptibility to diet-related diseases. This necessitates the identification of gene variants associated with differential responses to nutrients and with higher susceptibility to diet-related diseases. The ultimate goal of nutrigenetics is to provide nutritional recommendations for individuals in what is known as ''personalized'' or ''individualized nutrition''.
A number of companies have sprung up to cash in on the current popularity of genetic testing. Independent analysis of the service these companies deliver show that at best the advice delivered is highly generic, and at worst may lull the recipient into a false sense of security. As these companies are not offering specific clinical advice, they do not qualify for regulation beyond the accuracy of the genetic test applied. Retail boycotts in the UK have led to the voluntary suspension of industry activity, and in the US severe criticisms have been leveled by the [[Government Accountability Office]].
===Applications===
A number of genetic variations have been shown to increase the susceptibility to diet-related diseases. These include variants that have been associated with [[Type 2 diabetes mellitus]], [[obesity]], [[cardiovascular disease]]s, some [[autoimmune disease]]s and [[cancer]]s. Nutrigenetics aims to study these susceptible genes and provide dietary interventions for individuals at risk of such diseases. Some examples are shown below.
====Nutrigenetics and Type 2 Diabetes mellitus====
A number of genes are involved in regulating lipid metabolism and [[insulin sensitivity]], and thereby affecting the susceptibility to [[type 2 diabetes mellitus]]. Among them is the gene responsible for [[sterol response element binding protein]]-1c or SREBP-1c (a membrane-bound [[transcription factor]] which can directly activate the [[expression (genetics)|expression]] of several genes involved in the synthesis and uptake of cholesterol, [[fatty acids]], [[triglycerides]] and [[phospholipid]]s). In mice models, overexpression of SREBP-1c led to [[fatty liver]]s, [[hypertriglyceridemia]], severe [[insulin resistance]] and finally type 2 diabetes mellitus. Later, SREBP-1c was identified as a candidate gene in the regulation of human insulin resistance. Two [[missense mutations]] in [[exons]] coding the aminoterminal transcriptional activating domain of SREBP-1c were found in individuals displaying severe insulin resistance. Another association was found between an [[intron|intronic]] [[single nucleotide polymorphism]] ([[Cytosine|C]]/[[Thymine|T]]) between exons 18c and 19c and the onset of diabetes in men, but not in women. These studies suggest that mutations in SREBP-1c may increase the sensitivity to developing diabetes.
Furthermore, SREBP-1c appears to be susceptible to diet, and thus it can be a target for nutritional intervention. Studies in mice have shown that SREBP-1c [[mRNA]] expression was highly induced in mice having one polymorphism (–468 A/G) after the consumption of high [[fructose]] diets. This implies that a single nucleotide polymorphism can also modulate the sensitivity of a gene to dietary intervention.
====Nutrigenetics and cardiovascular diseases====
[[Hyperlipidemia]] is usually associated with [[atherosclerosis]] and [[coronary heart disease]]. Therapy includes lifestyle changes as alterations in the patient's diet, physical activity and treatment with [[pharmaceuticals]] such as [[statins]]. However, individuals respond differently to the treatment. This was attributed to genetic variations within the population. Genetic variations in genes encoding for [[apolipoprotein]]s, some [[enzymes]] and hormones can alter individual sensitivity to developing cardiovascular diseases. Some of these variants are susceptible for dietary intervention, for example:
* Individuals with the E4 [[allele]] in the [[apolipoprotein E]] gene show higher [[low-density lipoprotein]]-cholesterol (bad cholesterol) levels with increased dietary fat intake compared with those with the other (E1, E2, E3) alleles receiving equivalent amounts of dietary fat.
* One [[single nucleotide polymorphism]] (-75 [[Guanine|G]]/[[Adenine|A]]) in the [[apolipoprotein]] A1 gene in women is associated with an increase in [[High density lipoprotein]]-cholesterol levels with the increase in the dietary intake of [[polyunsaturated fatty acid]]s (PUFA). Individuals with the A variant showed an increase in the protective HDL (good cholesterol) levels following an increased consumption of PUFA compared with those with the G variant taking similar amounts of PUFA.
* One [[Polymorphism (biology)|polymorphism]] (-514 [[Cytosine|C]]C) in the hepatic [[lipase]] gene is associated with an increase in protective HDL levels compared with the [[Thymine|T]]T genotype (common in certain ethnic groups such as African-Americans) in response to high fat diet.
====Nutrigenetics and cancer====
Nutrients can contribute to the development of cancers especially [[colon cancer|colon]], [[Gastric cancer|gastric]] and [[Breast cancer|breast]] cancer. Several gene variants have been identified as susceptibility genes. One example is the [[N-Acetyltransferase]] (NAT) gene. NAT is a [[Drug metabolism|phase II metabolism]] enzyme that exists in two forms: NAT1 and NAT2. Several polymorphisms exist in NAT1 and NAT2, some of which have been associated with NAT capabilities of slow, intermediate or fast [[acetylation]]s. NAT is involved in acetylation of [[heterocyclic]] [[aromatic amines]] found in heated products especially well cooked red meat. During cooking of muscle meat at high temperature, some [[amino acids]] may react with [[creatine]] to give heterocyclic aromatic amines (HAA). HAA can be activated through acetylation to reactive metabolites which bind [[DNA]] and cause cancers. Only NAT2 fast acetylators can perform this acetylation. Studies have shown that the NAT2 fast acetylator genotype had a higher risk of developing colon cancer in people who consumed relatively large quantities of red meat.
== References ==
* Mutch DM et al. "Nutrigenomics and Nutrigenetics: the emerging faces of nutrition." FASEB J. 2005; 19:1602-1616.
* Ordovas JM and Mooser V. "Nutrigenomics and nutrigenetics." Curr Opin Lipidol. 2004 Apr;15(2):101-8.
* Gillies PJ. "Nutrigenomics: The Rubicon of molecular nutrition." J Am Diet Assoc. 2003; 103(12):S50-S55.
* Kaput J. "Diet-Disease Gene Interactions." Nutrition 2004; 20:26-31.
* Corthésy-Theulaz I et al. "Nutrigenomics: The Impact of Biomics Technology on Nutrition Research." Ann Nutr Metab 2005; 49:355-365.
* Brigelius-Flohe R and Joost HG (2006). "Nutritional genomics: Impact on health and disease". [[John Wiley & Sons|Wiley-VCH Verlag GmbH & co]], 3-17. ISBN 3-527-31294-3.
*Bijal Trivedi "Hungry genes?" New Scientist-20/01/2007;
== See also ==
* [[Genevestigator]]
* [[Orthomolecular medicine]]
* [[Roger J. Williams]]
[[Category:Nutrition]]
[[Category:Medical genetics]]
[[Category:Genomics]]
[[ru:Нутригеномика]]