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September 4, 2020
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Why Do Our Genes Cause Us To Be Metabolically Unique?

Differences in a person’s metabolism can derive from common variants in genes. People have more than 5 million variations in their genetic code (any individual person has about 50,000 of these single nucleotide polymorphisms (SNPs) that could change metabolism).  These gene variants are inherited from ancient ancestors, and therefore differ among people depending on their heritage. These gene variants can perturb the expression and function of enzymes, transporters or receptors and their ligands by changing the expression of the gene or the rate of translation of  messenger RNA (mRNA) into protein, by changing amino acid residues that affect the half-life of the protein(s), and/or by altering the protein’s structure thereby changing how an enzyme binds to its substrate and products.  These are called functional gene variants.  

There is a solid understanding of how functional SNPs alter the dietary requirements for the nutrient choline. The capacity to make choline from simpler chemicals is dependent on expression of the gene PEMT, and estrogen concentrations present in premenopausal and pregnant women are high enough that they can induce expression of this gene and this decreases how much they must depend on choline from their diets.  Men and postmenopausal women with low estrogen must be sure they get choline in their diets. A very common SNP in PEMT reduces PEMT’s inducibility by estrogen, and women with this SNP have an increased dietary choline requirement for choline; they are 25x more likely to develop liver or muscle damage when eating a low choline diet that are premenopausal women without this genetic variant.

Many other examples of gene variant effects on choline metabolism have been discovered. There are also good examples of how common gene variants alter a person’s requirements for Vitamin B12. For example, very high blood B12 concentrations are associated with variants in the gene FUT2.  This gene influences formation of the H antigen (a protein) – a precursor of the blood group A and B antigens.  How does changing the secretion of the H antigen alter B12 concentrations?  Bacteria that can disturb the stomach and gut environment, such as Helicobactor pylori , adhere to the stomach and gut cells with the help of the H antigen. Proper stomach acidity is needed for optimal B12 absorption from foods, and Helicobactor pylori disturbs acid secretion, thereby changing B12 processing.  When less H antigen is secreted (caused by the FUT2 gene variant), less bacteria are present, and more B12 is absorbed into a person’s blood.  Many other examples of gene variant effects on B12 levels in people have been discovered.  

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Words You May Not Know
Gene
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Gene

The gene is the basic physical unit of inheritance. Genes are passed from parents to offspring and contain the information needed to specify traits. Genes are arranged, one after another, on structures called chromosomes. A chromosome contains a single, long DNA molecule, only a portion of which corresponds to a single gene. Humans have approximately 20,000 genes arranged on their chromosomes.

SNPs
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SNPs

A Single Nucleotide Polymorphism is also known as a SNP or snp (pronounced 'snip'). The importance of SNPs comes from their ability to influence disease risk, drug efficacy and side-effects, tell you about your ancestry, and predict aspects of how you look and even act. SNPs are probably the most important category of genetic changes influencing common diseases. And in terms of common diseases, 9 of the top 10 leading causes of death have a genetic component and thus most likely one or more SNPs influence your risk.

mRNA
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mRNA

Messenger RNA (mRNA) is a single-stranded RNA molecule that is complementary to one of the DNA strands of a gene. The mRNA is an RNA version of the gene that leaves the cell nucleus and moves to the cytoplasm where proteins are made.

PEMT
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PEMT

PEMT stands for Phosphatidylethanolamine N-Methyltransferase. It is an enzyme that converts phosphatidylyethanolamine into phosphatidylycholine in the liver. The gene that codes for this enzyme is found on chromosome 17 in humans and is the site of frequent misspellings (or SNPs) that impact the function of the protein in this very important metabolic process to produce the phospholipid phoshatidylcholine.

FUT2 gene
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FUT2 gene

FUT2 stands for fucosyltransferase 2 and it is the gene that is responsible for modifying the antigens that affects the antigen characteristic of red blood cells (called the H Antigen) that contributes to the ABO blood group classification. Fucose is a sugar protein that is often added to a protein within the cell (in the golgi apparatus of the cell) to give it certain characteristics for its job.

Who Wrote This
Steven H. Zeisel MD PhD
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Dr. Zeisel is the Kenan Distinguished University Professor in the Department of Nutrition in the Gillings School of Global Public Health and School of Medicine at the University of North Carolina at Chapel Hill. Dr. Zeisel earned his MD from Harvard Medical School in 1975, was a resident in pediatrics at Yale University from 1975–1977 and earned his PhD in nutrition at the Massachusetts Institute of Technology in 1980. Dr. Zeisel is the Director of the UNC Nutrition Research Institute and Director of the UNC Nutrition and Obesity Research Center (one of 12 centers of excellence funded by the US NIH), North Carolina. Dr. Zeisel and his research team focus on the essential nutrient choline which is especially important during pregnancy and lactation, as choline is critical for brain and eye development. Dr. Zeisel has authored more than 380 scientific publications.

 

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