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.