Nutrition meets Genetics

One ongoing research is to develop food that can be matched to mine or your genotype to benefit our health and enhance normal physiological processes. This will lead to a personalized diet advice which may help to prevent monogenetic (=inherited disease controlled by a single pair of genes for example Cystic Fibrosis; Huntington’s Disease) and polygenetic diseases (=inherited and controlled by several genes at once for example cardiovascular diseases, high blood pressure, obesity, diabetes type II, Cancer, Osteoporosis and high cholesterol levels). It may sound science fiction right now cause until now all commercial companies ( e.g. Genelex, Sciona, TheDNADiet) who want to profit, just screen for 19 genes utilizing a multiplex technique that detects several SNPs ( Single Nucleotide Polymorphism, substitution of one nucleotide 1bp (point mutation) SNPs are located in regulatory sequences which belong to non coding region of the human genome. SNP could influence the transcription activity of other DNA regions. Most SNPs in that region have no effect.) simultaneously. This technique can be largely automated and is inexpensive. The 19 genes to be tested are coding for the following enzymes and proteins to mention a few MTHFR, PPARg, GSTM, VDR, IL-6, APOC 3. These are based on variations in the genes whereby they are not sufficient to give a personalized diet advice. The genes tested for SNP are involved in complex metabolic pathways. Current diet advices based on genetic tests don’t take complex metabolic pathways into account. After all there is lots of research needed.

The aim is to look for an approach that helps to solve the biochemical mechanism by which nutritional components like fatty acids influence health. One method is to use oligonucleotide microarrays to measure gene expression profiles of healthy individuals who regularly consume fish oil enriched with Ω-3 to individuals with no fish oil consumption. The results will show effects of fatty acids and other components in fish oil on gene expression, although for the greater amount of genes detected the exact function remains now unknown. What we benefit are genomic signatures that are associated with certain nutrients, diets or diseases. One can consider it as a fingerprint of a physiological or pathophysiological state or fingerprint of the phenotype.

In general the phenotype is determined by the genotype and external factors as lifestyle and nutritrition. Therefore it is possible that a certain genotype (polymorphism) leads in different people to different phenotypes.

Sometimes there is a clear relation between genotype, phenoype and effects of certain nutrients. Most times the relation between genotype, external factors and phenotype are complex. For example coronary heart disease is determined by the interaction of several genes and polymorphism of those genes including external factors. They are polygenetic complex diseases,also not all genetic factors are known to give a personalized diet advice.

In all there is a lot more to know about nutrition, genes and metabolic diseases.

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Nutrizymes through the looking glass

These are mostly enzymes or proteins that are involved in several metabolic activities and are coded by the genes that are tested to give a personalized diet advice. Changes in the corresponding gene leads to changes in expression that is not always to be seen negative.
I would like to introduce a few which are included  to give a personalized diet advice: MTHFR, PPARγ, VDR, IL-6, APOC3, GSTM

MTHFR Methylenetetrahydrofolate reductase

MTHFR is involved in the folate metabolism. It serves as a methyl donor for remethylating homocysteine to methionine (= non essential Amino acid).This requires Vitamin B12.

Increased levels of homocysteine lead to a greater risk for heart diseases.

The following variations of this gene are observed.

MTHFR gene variation
Genotype MTHFR activity Explanation
TT Lowest; Lowest bioavailability No change of proximity to heart disease with Vitamin B12 & folic acid supplements
CC Normal No Vitamin supplements needed
CT Lower; Lower MTHFR bioavailability Less methionine synthesis, but with increased Vitamin B12 intake -> heart disease risk less

PPARγ / PPARg      Peroxisome proliferator activated receptor gamma

Member of the nuclear hormone receptor subfamily of transcription factors where fatty acids are their natural ligands. PPARs form heterodimers with retinoid x receptors and these heterodimers regulate transcription of various genes. It is believed that PPARg is believed to be involved in adipocyte differentiation cause it is expressed in high concentrations within the adipocyte and large intestine while lower expression levels are in the bone marrow, spleen, testis, brain and liver. An important polymorphism in the PPARg gene is the Pro12Ala.

The variation Pro12Ala in the PPARg gene is beneficial. It is associated with a reduced risk for diabetes and heart diseases.

GSTM Glutathione 5 -transferase mu

Its function relies in the detoxification of carcinogens, therapeutic drugs, environment toxins and products of oxidative stress. Genetic variations can change the individuals susceptibility to carcinogen and toxins as well as effect the toxicity and efficacy of certain drugs.

The polymorphism of GSTM gene are due to deletions of a part of a gene which in turn results into a lower enzyme activity and is associated with a higher risk towards cancer and autoimmune diseases.

VDR Vitamin D receptor

Functions as transcription factor that specifically binds to derivatives of Vitamin D (= 1,25 Dihydroxycholcalciferol) and mediates processes involved in bone health.

IL-6  Interleukin 6

Members of cytokines. (= small proteins that play a role during inflammation caused by bacteria, viruses or metabolic stress) Interleukins are produced and secreted by leukocytes (=White blood cells). Interleukins in general bind to the cell membrane, some interleukins have pro-inflammatory effects while others anti-inflammatory.

APOC 3 apolioprotein C-III

The gene in question encodes part of the lipoprotein that transport lipids in the plasma and are important to the lipid metabolism. A substitution of one nucleotide by another in the APOC 3 gene is associated with a high triacylglycerol concentration in the plasma which can lead to arteriosclerosis and coronary heart diseases.

Variations due to substitution of one gene to another which is a characteristic towards SNP (=Single Nucleotide Polymorphism) are following macromolecules: MTHFR, VDR,     APOC 3, IL-6.

Variations due to deletion of part of the gene belongs to GSTM.

Metabolic activity with gene variation
Metabolic activity Gene variation(s) involved
Insulin sensitivity PPAR
Heart health MTHFR; PPAR; APOC-3;IL-6
Detoxification GSTM
Antioxidant activity GSTM
B-Vitamin use MTHFR
Bone health VDR; IL-6
Inflammation IL-6

Some variations in the gene give rise to specific diet advice as the following show:

Specific diet advice and corresponding gene variation with metabolic condition
Specific diet advice Gene variation
Eat food rich in Vitamin B12 MTHFR gene
High fruit & vegetables consume MTHFR; APOC-3;IL-6; GSTM influences heart health & antioxidant activity
Eat food rich in Calcium & Vitamin D VDR gene affecting bone health
Limit Cholesterol intake APOC-3 increasing risk of heart health

We can conclude that some advices are specific and based on variations found in one gene regarding MTHFR, while most advices are very general and are also important when no specific variations are found. Nutritional foods are complex and consist of various macro- and micronutrients. Foods that contain Vitamin B9 contain also other Vitamins of which the health effect is unknown. Also not everything about the interaction between the different components in food is known.

There is a lot of research going on and it is just a matter of time  to be able to develop foods that can be matched to an individuals genotype to benefit the health and enhance normal physiological processes.

Reference

http://www.nugo.org

e-learning – Molecular Nutrition and Nutrigenomics

Learning about the emerging science of Nutrigenomics

It has been a month since I subscribed myself to the certified e-online course offered by the European Nutrigenomics Organisation (NuGO).It is a network connecting researchers from across Europe and beyond to work together and share their expertise upon linking genomics and nutrition with research on health.

Nutrigenomics can be defined as the study between food constituents (macronutients and micronutrients)and its effect on gene expression. Many articles show that nutritional supplements improve many metabolic abnormalities by enhancing specific biochemical pathways. The aim is to find genetic markers that have an impact on diet related diseases like diabetes type 2, obesity etc..
There are already several association studies available that explain to which extent an individual is susceptible for the development of that disease, once a marker has been found and analyzed, personalized dietary recommendations can be given to the patients that are most likely to be effective with less implications and side reactions that affect a patient in a negative way

Through enrollment to 2 training courses (Molecular Nutrition and Genomics, Polymorphism and Responsiveness to Diet) I have access to the NuGO site for 3 months. Weekly I get newsletters from renowned scientific and medical magazines and read about newly published articles.
Though the Courses are directed towards dietitians and Nutritioners to explore the emerging science of nutrigenomics, it invites also other work fields related to biological science or equivalent to participate and contribute to the NuGO community.

What I learned from NuGO so far,What You can learn, benefit

New findings in nutrigenomics will be important because testing for associated genes may be useful for advising personal diets based on genetic tests.
There are several companies around the world profiting from consumers by giving them the illusions of advising personalized diets through testing the consumers genes. The fact that remains unsaid is that all testing constitutes of screening for variations in 19 genes, which is less than 0.1% of all the genes ( approximately 30000 genes in human).There are many more (unknown) variations which could be important for a personalized diet advice but these are ignored by those companies. These so called advertised personalized diets are in fact general diets and are nearly advising the same as the dietary guidelines of “The American Hearth Association”. Other companies base their advice on results of lifestyle and food questionnaires the customer filled in. This advice is of course personal, but not based on the genome. Some times such advice is called personalized diet advice. However, most of the time this advice is called tailored advice. Before I visited NuGO I was myself lured into that lie believing that it is true and not thinking about the idea that people do market the idea of testing the individual’s genetic makeup. For myself as an emerging biotechnologist I found those topics very much interesting and wanted to learn more about it, this way I can profit from the new knowledge that I acquire and expand thereof my scientific know-how in nutrigenomics and biotechnology.

http://www.nugo.org