Member - Academy Of Nutrition & Dietetics. USA.
Nutrigenetics / Genomics
Often we find identical twins with dissimilar characteristics and different physical structure. Though nutrition professionals were initially astounded by this fact they have realized that nutrition and lifestyle choices have major impact on genetic makeup. While physicians have been treating diseases for the past 50 years, the focus has been shifted to intervening and preventing these diseases by understanding the genes and environmental factors responsible for them.
Nutrition experts link a genotype, a person’s unique genetic constitution, with that individual’s susceptibility to a particular disease. A stage would arise when patients would be carrying their genetic profile with them while visiting the nutrition specialist. These specialists would also be equipped to read the genotypes and become aware of the client’s susceptibility to certain diseases and the remedy for reducing their occurrence.
Genetic Fundamentals
Genetics and Genomics: Nutrigenetics and Nutrigenomics
Genetics is the science of inheritance. Originally genetics focused on understanding the principle through which physical traits and certain rare diseases were passed over generations. Off late geneticists realize that, all diseases are directly or indirectly connected with the information in the genes. Nutrigenetics concerns the study of how an individual’s particular genetic variants affect functions and response to nutrients.
Genome is an organism’s complete genetic information. Genomics, a discipline of genetics, analyzes the function and structure of genomes. It concentrates on the chronic diseases that are due to multiple genes and other factors. Nutritional genomics or nutrigenomics is the study of the impact of nutrients and other biologically active food components on gene expression.
Genetics and Nutrition Therapy
Diseases occur at the chromosomal, mitochondrial and molecular levels. Genetic metabolic disorders and sex-linked disorders are also common. Nutrition experts have been curing people affected by these diseases since a long time. Nutritional genomics plays a pivotal role in expanding the role of these experts beyond these diseases and into more serious chronic ailments such as cancer, diabetes, cardiovascular disease and many others.
Experiments in knowing the gene variants involved in particular chronic diseases and the interaction of bioactive food components associated with these variants have led to nutrition specialists link the findings to relevant nutrition intervention. Bioactive food components alter genetic outcomes in two ways: by influencing metabolic processes or by influencing gene outcomes.
Nutritional Genomic Influences on Metabolic Processes
The association between nutrition and genetics is simple yet complex. A faulty gene, a defective protein, a deficient level of a metabolite and a resultant disease that is passed on through inheritance responds to nutrition therapy proving the simple relationship between nutrition and genetics. Our body cannot produce certain amino acids, fatty acids, vitamins and minerals naturally and we have to depend on external diet for these nutrients to stay away from diseases and dysfunctions.
Deoxyribonucleic acid (DNA) is the genetic or hereditary material in all living organisms. It has a two-stranded chemical structure and known as ‘double helix’. The entire DNA instruction book, or genome, for a human being has about 3 billion bases and 20,000 genes on 23 pairs of chromosomes. DNA molecule carries all the biological information required for life. Any small change in the DNA molecule can result in diseases. Enzymes read the information in DNA and transcribe it into an intermediary molecule called mRNA. Cofactors are helper molecules of enzymes which assist in biochemical transformations. Around 50 metabolic reactions in which there is decreased affinity between the enzyme and its cofactor have been identified. Complex nutrients are required in these situations to restore functions. The amount of nutrients required differs for each individual. One person may require more than normal levels of a nutrient because of their genetic makeup while another person may internally produce the required levels of the nutrient preventing the need for any additional supplementation.
The best example which supports the fact that genetic variations can affect nutritional requirements is the enzyme MTHFR that affects folate metabolism. Folate is primarily involved in carrying and activating one-carbon units. The one-carbon units are carried on the N-5 or N-10 of tetrahydrofolate. Methionine is adenylated to form S-adenosylmethionine, a methyl donor to various metabolic reactions, including the ones involved in synthesizing nucleic acid. The 677C>T gene variant is the most common variation of the MTHFR gene and involves substitution of thymine for cytosine at position 677.The resulting enzyme is thermolabile which has reduced activity, causing homocysteine to accumulate. Folate deficiency increases the risk of neural tube defects and CVDs. Including folate supplements can nullify the effects of the gene variation and protect individuals against these diseases. Surprisingly the same MTHFR mutation is said to be protective against several types of cancers, especially colon cancer. Transport of iron or copper to levels higher than the normal range specified because of mutations generally have nutritional implications. Vitamin D mutations not only affect bone health but the entire body as well, since vitamin D is involved in multiple metabolic and regulatory processes. Mutations in gene coding for insulin can result in dysglycemia. Several proteins such as kinases, cytokines and transcription factors also undergo mutations and end up in altered activities.
Nutritional Genomic Influences on Gene Expression
The fact that bioactive food components and nutrients influence gene expression is true in the case of both lower organisms and higher organisms. A classic example is the response of cells to glucose levels. A drop in blood sugar levels triggers epinephrine and glucagon release which through signal transduction stimulates glycogen breakdown to glucose and restores blood sugar levels. Nutrients and bioactive food components also act as ligands, molecules that bind to certain sequences within a gene’s regulatory region. Gene expressions change due to binding through transcription process. Polyunsaturated omega-3 fatty acids can be taken as an example of a ligand. These fats serve to decrease inflammation by reducing the expression of key genes responsible for inflammatory cytokines production such as tumor necrosis factor-α and the interleukin-1 family of genes. Omega-3 and omega-6 fatty acids play the role of ligands for the peroxisome proliferator-activated receptor (PPAR) transcription factors. PPARs assist in lipid metabolism, glucose homeostasis and cell proliferation. They also play a key role in insulin resistance and obesity.
PPARgamma isoform plays a crucial role in gene expression. Retinoic X receptor (RXR) and PPARgamma are two famous receptors of the 48-member nuclear family of receptors. Ligands of these receptors are provided in the form of diet or made endogenously, such as cholesterol, steroid hormones, bile acids and active forms of vitamin D.
Complex Genetic-Nutrition Connections
DNA changes are foolproof in single gene disorders and the resulting phenotype is clearly defined. Chronic diseases involve multiple genes with each gene having many variations and contributing a little to the overall resulting disease rather than a single gene having a drastic impact on the disorder. Phenotypes are also affected by environmental factors. All these along with nutrition and lifestyle choices decide the liability of an individual to a disorder.
Genetic Variability
When disorders are affected by multiple genes and environmental factors it becomes a mountainous task for the nutrition specialist to work on the heterogeneity of responses from the patients to the same therapeutic approach. The positive fact here is that only the magnitude of response varies and no critical problems arise because of these factors. The focus of research now is to identify disease susceptibility and formulate strategies for disease prevention specifically targeted to the underlying genetic mechanism. Discussed below are few primary diet-related genes, their variants and the effect of these variants on a person’s response to diet.
Cardiovascular Disease
Nutrition specialists working with dyslipidemia patients have observed huge variations in response to the same dietary recommendation. The therapies recommended decrease LDL cholesterol (LDL-C) and triglyceride (TGs) and raise HDL cholesterol (HDL-C) levels. The dietary recommendations insist on lowering fat and cholesterol intake and increasing polyunsaturated fatty acid intake. Response was quite varied with lowered LDL-C levels and TGs in some, decreased HDL-C levels to elevated TGs in few others. Some patients showed drastically reduced LDL-C levels after consuming dietary oat bran and other soluble fibers while others had modest outcomes after consuming these. These clearly indicate that the genetic makeup of an individual plays a vital role in deciding the response to nutrition therapies and hence diets should match the genotype to maximize lipid-lowering responses. A number of such genes have already been identified and are being studied. As cardiovascular disease is an inflammatory disorder variants of genes such as TNF-α and IL1 and IL6 affect cardiovascular susceptibility.
Cancer
Many gene-diet researches are ongoing for carcinogenesis. The body protects against cancer through detoxification. Cytochrome P450 isozyme (CYPs), glutathione S-transferases (GSTs) and superoxide dismutases (SOD1, SOD2, SOD3) are better-characterized genes involved in detoxification. Few variants of these genes have been identified which cause decreased detoxification. Nutritional genomics helps to analyse the genotype of an individual and administering nutrition therapy such that it gives protection against cancer by intensifying detoxification activity.
Other Chronic Diseases
Research is ongoing for other chronic diseases such as type 2 diabetes, osteoporosis and obesity. As genetic makeover varies with each individual and health implications arise based on these variations, researchers are trying to identify frequency of particular variants among populations. This helps to simplify dietary modifications and provide effective diet plans for a common population.
Often we find identical twins with dissimilar characteristics and different physical structure. Though nutrition professionals were initially astounded by this fact they have realized that nutrition and lifestyle choices have major impact on genetic makeup. While physicians have been treating diseases for the past 50 years, the focus has been shifted to intervening and preventing these diseases by understanding the genes and environmental factors responsible for them.
Nutrition experts link a genotype, a person’s unique genetic constitution, with that individual’s susceptibility to a particular disease. A stage would arise when patients would be carrying their genetic profile with them while visiting the nutrition specialist. These specialists would also be equipped to read the genotypes and become aware of the client’s susceptibility to certain diseases and the remedy for reducing their occurrence.
Genetic Fundamentals
Genetics and Genomics: Nutrigenetics and Nutrigenomics
Genetics is the science of inheritance. Originally genetics focused on understanding the principle through which physical traits and certain rare diseases were passed over generations. Off late geneticists realize that, all diseases are directly or indirectly connected with the information in the genes. Nutrigenetics concerns the study of how an individual’s particular genetic variants affect functions and response to nutrients.
Genome is an organism’s complete genetic information. Genomics, a discipline of genetics, analyzes the function and structure of genomes. It concentrates on the chronic diseases that are due to multiple genes and other factors. Nutritional genomics or nutrigenomics is the study of the impact of nutrients and other biologically active food components on gene expression.
Genetics and Nutrition Therapy
Diseases occur at the chromosomal, mitochondrial and molecular levels. Genetic metabolic disorders and sex-linked disorders are also common. Nutrition experts have been curing people affected by these diseases since a long time. Nutritional genomics plays a pivotal role in expanding the role of these experts beyond these diseases and into more serious chronic ailments such as cancer, diabetes, cardiovascular disease and many others.
Experiments in knowing the gene variants involved in particular chronic diseases and the interaction of bioactive food components associated with these variants have led to nutrition specialists link the findings to relevant nutrition intervention. Bioactive food components alter genetic outcomes in two ways: by influencing metabolic processes or by influencing gene outcomes.
Nutritional Genomic Influences on Metabolic Processes
The association between nutrition and genetics is simple yet complex. A faulty gene, a defective protein, a deficient level of a metabolite and a resultant disease that is passed on through inheritance responds to nutrition therapy proving the simple relationship between nutrition and genetics. Our body cannot produce certain amino acids, fatty acids, vitamins and minerals naturally and we have to depend on external diet for these nutrients to stay away from diseases and dysfunctions.
Deoxyribonucleic acid (DNA) is the genetic or hereditary material in all living organisms. It has a two-stranded chemical structure and known as ‘double helix’. The entire DNA instruction book, or genome, for a human being has about 3 billion bases and 20,000 genes on 23 pairs of chromosomes. DNA molecule carries all the biological information required for life. Any small change in the DNA molecule can result in diseases. Enzymes read the information in DNA and transcribe it into an intermediary molecule called mRNA. Cofactors are helper molecules of enzymes which assist in biochemical transformations. Around 50 metabolic reactions in which there is decreased affinity between the enzyme and its cofactor have been identified. Complex nutrients are required in these situations to restore functions. The amount of nutrients required differs for each individual. One person may require more than normal levels of a nutrient because of their genetic makeup while another person may internally produce the required levels of the nutrient preventing the need for any additional supplementation.
The best example which supports the fact that genetic variations can affect nutritional requirements is the enzyme MTHFR that affects folate metabolism. Folate is primarily involved in carrying and activating one-carbon units. The one-carbon units are carried on the N-5 or N-10 of tetrahydrofolate. Methionine is adenylated to form S-adenosylmethionine, a methyl donor to various metabolic reactions, including the ones involved in synthesizing nucleic acid. The 677C>T gene variant is the most common variation of the MTHFR gene and involves substitution of thymine for cytosine at position 677.The resulting enzyme is thermolabile which has reduced activity, causing homocysteine to accumulate. Folate deficiency increases the risk of neural tube defects and CVDs. Including folate supplements can nullify the effects of the gene variation and protect individuals against these diseases. Surprisingly the same MTHFR mutation is said to be protective against several types of cancers, especially colon cancer. Transport of iron or copper to levels higher than the normal range specified because of mutations generally have nutritional implications. Vitamin D mutations not only affect bone health but the entire body as well, since vitamin D is involved in multiple metabolic and regulatory processes. Mutations in gene coding for insulin can result in dysglycemia. Several proteins such as kinases, cytokines and transcription factors also undergo mutations and end up in altered activities.
Nutritional Genomic Influences on Gene Expression
The fact that bioactive food components and nutrients influence gene expression is true in the case of both lower organisms and higher organisms. A classic example is the response of cells to glucose levels. A drop in blood sugar levels triggers epinephrine and glucagon release which through signal transduction stimulates glycogen breakdown to glucose and restores blood sugar levels. Nutrients and bioactive food components also act as ligands, molecules that bind to certain sequences within a gene’s regulatory region. Gene expressions change due to binding through transcription process. Polyunsaturated omega-3 fatty acids can be taken as an example of a ligand. These fats serve to decrease inflammation by reducing the expression of key genes responsible for inflammatory cytokines production such as tumor necrosis factor-α and the interleukin-1 family of genes. Omega-3 and omega-6 fatty acids play the role of ligands for the peroxisome proliferator-activated receptor (PPAR) transcription factors. PPARs assist in lipid metabolism, glucose homeostasis and cell proliferation. They also play a key role in insulin resistance and obesity.
PPARgamma isoform plays a crucial role in gene expression. Retinoic X receptor (RXR) and PPARgamma are two famous receptors of the 48-member nuclear family of receptors. Ligands of these receptors are provided in the form of diet or made endogenously, such as cholesterol, steroid hormones, bile acids and active forms of vitamin D.
Complex Genetic-Nutrition Connections
DNA changes are foolproof in single gene disorders and the resulting phenotype is clearly defined. Chronic diseases involve multiple genes with each gene having many variations and contributing a little to the overall resulting disease rather than a single gene having a drastic impact on the disorder. Phenotypes are also affected by environmental factors. All these along with nutrition and lifestyle choices decide the liability of an individual to a disorder.
Genetic Variability
When disorders are affected by multiple genes and environmental factors it becomes a mountainous task for the nutrition specialist to work on the heterogeneity of responses from the patients to the same therapeutic approach. The positive fact here is that only the magnitude of response varies and no critical problems arise because of these factors. The focus of research now is to identify disease susceptibility and formulate strategies for disease prevention specifically targeted to the underlying genetic mechanism. Discussed below are few primary diet-related genes, their variants and the effect of these variants on a person’s response to diet.
Cardiovascular Disease
Nutrition specialists working with dyslipidemia patients have observed huge variations in response to the same dietary recommendation. The therapies recommended decrease LDL cholesterol (LDL-C) and triglyceride (TGs) and raise HDL cholesterol (HDL-C) levels. The dietary recommendations insist on lowering fat and cholesterol intake and increasing polyunsaturated fatty acid intake. Response was quite varied with lowered LDL-C levels and TGs in some, decreased HDL-C levels to elevated TGs in few others. Some patients showed drastically reduced LDL-C levels after consuming dietary oat bran and other soluble fibers while others had modest outcomes after consuming these. These clearly indicate that the genetic makeup of an individual plays a vital role in deciding the response to nutrition therapies and hence diets should match the genotype to maximize lipid-lowering responses. A number of such genes have already been identified and are being studied. As cardiovascular disease is an inflammatory disorder variants of genes such as TNF-α and IL1 and IL6 affect cardiovascular susceptibility.
Cancer
Many gene-diet researches are ongoing for carcinogenesis. The body protects against cancer through detoxification. Cytochrome P450 isozyme (CYPs), glutathione S-transferases (GSTs) and superoxide dismutases (SOD1, SOD2, SOD3) are better-characterized genes involved in detoxification. Few variants of these genes have been identified which cause decreased detoxification. Nutritional genomics helps to analyse the genotype of an individual and administering nutrition therapy such that it gives protection against cancer by intensifying detoxification activity.
Other Chronic Diseases
Research is ongoing for other chronic diseases such as type 2 diabetes, osteoporosis and obesity. As genetic makeover varies with each individual and health implications arise based on these variations, researchers are trying to identify frequency of particular variants among populations. This helps to simplify dietary modifications and provide effective diet plans for a common population.