Nutritional genomics
Encyclopedia
Nutritional genomics is a science studying the relationship between human genome, nutrition and health.
It can be divided into two disciplines:
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, many common diseases, such as 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.
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.
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.
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.
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 begun offering nutrigenetic testing, but the recommendations are often highly generic, and could provide 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. Objections to such testing kits in the UK have led to the voluntary suspension of commercial testing activity there, and in the US severe criticisms have been leveled against various testing companies by the Government Accountability Office
.
, 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.
which can directly activate the 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
ic single nucleotide polymorphism
(C
/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.
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:
. Several gene variants have been identified as susceptibility genes. One example is the N-Acetyltransferase
(NAT) gene. NAT is a 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 amine
s 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.
http://nutritional-genomics.com
It can be divided into two disciplines:
- NutrigenomicsNutrigenomicsNutrigenomics is the study of the effects of foods and food constituents on gene expression. It is about how our DNA is transcribed into mRNA and then to proteins and provides a basis for understanding the biological activity of food components...
: studies the effect of nutrients on health through altering genomeGenomeIn modern molecular biology and genetics, the genome is the entirety of an organism's hereditary information. It is encoded either in DNA or, for many types of virus, in RNA. The genome includes both the genes and the non-coding sequences of the DNA/RNA....
, proteomeProteomeThe proteome is the entire set of proteins expressed by a genome, cell, tissue or organism. More specifically, it is the set of expressed proteins in a given type of cells or an organism at a given time under defined conditions. The term is a portmanteau of proteins and genome.The term has been...
, metabolomeMetabolomeMetabolome refers to the complete set of small-molecule metabolites to be found within a biological sample, such as a single organism...
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. More specifically, nutrigenomics studies how individual differences in genesGênesGênes is the name of a département of the First French Empire in present Italy, named after the city of Genoa. It was formed in 1805, when Napoleon Bonaparte occupied the Republic of Genoa. Its capital was Genoa, and it was divided in the arrondissements of Genoa, Bobbio, Novi Ligure, Tortona and...
influence the body's response to dietDiet (nutrition)In nutrition, diet is the sum of food consumed by a person or other organism. Dietary habits are the habitual decisions an individual or culture makes when choosing what foods to eat. With the word diet, it is often implied the use of specific intake of nutrition for health or weight-management...
and nutritionNutritionNutrition is the provision, to cells and organisms, of the materials necessary to support life. Many common health problems can be prevented or alleviated with a healthy diet....
. For example, people with an enzymeEnzymeEnzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
deficiency caused by mutations in the enzyme phenylalanine hydroxylasePhenylalanine hydroxylasePhenylalanine hydroxylase is an enzyme that catalyzes the hydroxylation of the aromatic side-chain of phenylalanine to generate tyrosine. PheOH is one of three members of the pterin-dependent amino acid hydroxylases, a class of monooxygenase that uses tetrahydrobiopterin and a non-heme iron for...
cannot metabolize foods containing the amino acidAmino acidAmino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...
phenylalaninePhenylalaninePhenylalanine is an α-amino acid with the formula C6H5CH2CHCOOH. This essential amino acid is classified as nonpolar because of the hydrophobic nature of the benzyl side chain. L-Phenylalanine is an electrically neutral amino acid, one of the twenty common amino acids used to biochemically form...
and must modify their diets to minimize consumptionIngestionIngestion is the consumption of a substance by an organism. In animals, it normally is accomplished by taking in the substance through the mouth into the gastrointestinal tract, such as through eating or drinking...
. With modern genomic data, severe gene mutations with less severe effects are being explored to determine whether dietary practices can be more closely personalized to individual genetic profiles. However, there have been few validated studies for these kinds of classical gene mutation effects.
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 monogenicMonogenic
Monogenic may refer to:* Monogenic * Monogenic field in algebraic number theory* Monogenic semigroup as an algebraic structure* Monogenic signal in the theory of analytic signals* Monogenic system in classical mechanics...
diseases. One example is phenylketonuria
Phenylketonuria
Phenylketonuria is an autosomal recessive metabolic genetic disorder characterized by a mutation in the gene for the hepatic enzyme phenylalanine hydroxylase , rendering it nonfunctional. This enzyme is necessary to metabolize the amino acid phenylalanine to the amino acid tyrosine...
, a genetic disease characterized by a defective phenylalanine hydroxylase
Phenylalanine hydroxylase
Phenylalanine hydroxylase is an enzyme that catalyzes the hydroxylation of the aromatic side-chain of phenylalanine to generate tyrosine. PheOH is one of three members of the pterin-dependent amino acid hydroxylases, a class of monooxygenase that uses tetrahydrobiopterin and a non-heme iron for...
enzyme, which is normally responsible for the metabolism of phenylalanine
Phenylalanine
Phenylalanine is an α-amino acid with the formula C6H5CH2CHCOOH. This essential amino acid is classified as nonpolar because of the hydrophobic nature of the benzyl side chain. L-Phenylalanine is an electrically neutral amino acid, one of the twenty common amino acids used to biochemically form...
to tyrosine
Tyrosine
Tyrosine or 4-hydroxyphenylalanine, is one of the 22 amino acids that are used by cells to synthesize proteins. Its codons are UAC and UAU. It is a non-essential amino acid with a polar side group...
. This results in the accumulation of phenylalanine and its breakdown products in the blood and the decrease in tyrosine
Tyrosine
Tyrosine or 4-hydroxyphenylalanine, is one of the 22 amino acids that are used by cells to synthesize proteins. Its codons are UAC and UAU. It is a non-essential amino acid with a polar side group...
, 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, many common diseases, such as 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
Transcription factor
In molecular biology and genetics, a transcription factor is a protein that binds to specific DNA sequences, thereby controlling the flow of genetic information from DNA to mRNA...
s, or through the secretion of hormones that in turn interfere with a transcription factor.
Nutrigenomics
NutrigenomicsNutrigenomics
Nutrigenomics is the study of the effects of foods and food constituents on gene expression. It is about how our DNA is transcribed into mRNA and then to proteins and provides a basis for understanding the biological activity of food components...
refers to the prospective analysis of differences among nutrients in the regulation of gene expression
Gene expression
Gene expression is the process by which information from a gene is used in the synthesis of a functional gene product. These products are often proteins, but in non-protein coding genes such as ribosomal RNA , transfer RNA or small nuclear RNA genes, the product is a functional RNA...
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
DNA microarray
A DNA microarray is a collection of microscopic DNA spots attached to a solid surface. Scientists use DNA microarrays to measure the expression levels of large numbers of genes simultaneously or to genotype multiple regions of a genome...
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 projectHuman Genome Project
The Human Genome Project is an international scientific research project with a primary goal of determining the sequence of chemical base pairs which make up DNA, and of identifying and mapping the approximately 20,000–25,000 genes of the human genome from both a physical and functional...
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
Metabolomics
Metabolomics is the scientific study of chemical processes involving metabolites. Specifically, metabolomics is the "systematic study of the unique chemical fingerprints that specific cellular processes leave behind", the study of their small-molecule metabolite profiles...
) and protein (proteomics
Proteomics
Proteomics is the large-scale study of proteins, particularly their structures and functions. Proteins are vital parts of living organisms, as they are the main components of the physiological metabolic pathways of cells. The term "proteomics" was first coined in 1997 to make an analogy with...
) levels.
Genomic and transcriptomic studies are mostly conducted by DNA microarray
DNA microarray
A DNA microarray is a collection of microscopic DNA spots attached to a solid surface. Scientists use DNA microarrays to measure the expression levels of large numbers of genes simultaneously or to genotype multiple regions of a genome...
technologies. Proteomics and metabolomics have no standardized procedures yet, but usually, proteome analysis is done by two-dimensional gel electrophoresis
Two-dimensional gel electrophoresis
Two-dimensional gel electrophoresis, abbreviated as 2-DE or 2-D electrophoresis, is a form of gel electrophoresis commonly used to analyze proteins...
and Liquid chromatography-mass spectrometry
Liquid chromatography-mass spectrometry
Liquid chromatography–mass spectrometry is an analytical chemistry technique that combines the physical separation capabilities of liquid chromatography with the mass analysis capabilities of mass spectrometry. LC-MS is a powerful technique used for many applications which has very high...
, while metabolome analysis is conducted through gas chromatography-mass spectrometry
Gas chromatography-mass spectrometry
Gas chromatography–mass spectrometry is a method that combines the features of gas-liquid chromatography and mass spectrometry to identify different substances within a test sample. Applications of GC-MS include drug detection, fire investigation, environmental analysis, explosives investigation,...
, liquid chromatography-mass spectrometry
Liquid chromatography-mass spectrometry
Liquid chromatography–mass spectrometry is an analytical chemistry technique that combines the physical separation capabilities of liquid chromatography with the mass analysis capabilities of mass spectrometry. LC-MS is a powerful technique used for many applications which has very high...
and liquid chromatography-nuclear magnetic resonance
Nuclear magnetic resonance
Nuclear magnetic resonance is a physical phenomenon in which magnetic nuclei in a magnetic field absorb and re-emit electromagnetic radiation...
.
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 a study that simultaneously identified a mechanism for the regulation of sterolSterol
Sterols, also known as steroid alcohols, are a subgroup of the steroids and an important class of organic molecules. They occur naturally in plants, animals, and fungi, with the most familiar type of animal sterol being cholesterol...
uptake in the intestine and the basis for sitosterolemia
Sitosterolemia
Sitosterolemia is a rare autosomal recessively inherited lipid metabolic disorder. It is characterized by hyperabsorption and decreased biliary excretion of dietary sterols leading to hypercholesterolemia, tendon and tuberous xanthomas, premature development of atherosclerosis, and abnormal...
(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
Lipid metabolism
Lipid metabolism refers to the processes that involve the intercourse and degradation of lipids.The types of lipids involved include:* Bile salts* Cholesterols* Eicosanoids* Glycolipids* Ketone bodies* Fatty acids - see also fatty acid metabolism...
-altering drug and DNA microarray technology was used for mRNA expression profiling
Expression profiling
In the field of molecular biology, gene expression profiling is the measurement of the activity of thousands of genes at once, to create a global picture of cellular function. These profiles can, for example, distinguish between cells that are actively dividing, or show how the cells react to a...
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
Cholesterol
Cholesterol is a complex isoprenoid. Specifically, it is a waxy steroid of fat that is produced in the liver or intestines. It is used to produce hormones and cell membranes and is transported in the blood plasma of all mammals. It is an essential structural component of mammalian cell membranes...
, 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 genetic makeupGenotype
The genotype is the genetic makeup of a cell, an organism, or an individual usually with reference to a specific character under consideration...
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 begun offering nutrigenetic testing, but the recommendations are often highly generic, and could provide 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. Objections to such testing kits in the UK have led to the voluntary suspension of commercial testing activity there, and in the US severe criticisms have been leveled against various testing companies by the Government Accountability Office
Government Accountability Office
The Government Accountability Office is the audit, evaluation, and investigative arm of the United States Congress. It is located in the legislative branch of the United States government.-History:...
.
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, obesityObesity
Obesity is a medical condition in which excess body fat has accumulated to the extent that it may have an adverse effect on health, leading to reduced life expectancy and/or increased health problems...
, cardiovascular disease
Cardiovascular disease
Heart disease or cardiovascular disease are the class of diseases that involve the heart or blood vessels . While the term technically refers to any disease that affects the cardiovascular system , it is usually used to refer to those related to atherosclerosis...
s, some autoimmune disease
Autoimmune disease
Autoimmune diseases arise from an overactive immune response of the body against substances and tissues normally present in the body. In other words, the body actually attacks its own cells. The immune system mistakes some part of the body as a pathogen and attacks it. This may be restricted to...
s and cancer
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
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 factorTranscription factor
In molecular biology and genetics, a transcription factor is a protein that binds to specific DNA sequences, thereby controlling the flow of genetic information from DNA to mRNA...
which can directly activate the expression of several genes involved in the synthesis and uptake of cholesterol, fatty acids, triglycerides and phospholipid
Phospholipid
Phospholipids are a class of lipids that are a major component of all cell membranes as they can form lipid bilayers. Most phospholipids contain a diglyceride, a phosphate group, and a simple organic molecule such as choline; one exception to this rule is sphingomyelin, which is derived from...
s). In mice models, overexpression of SREBP-1c led to fatty liver
Fatty liver
Fatty liver, also known as fatty liver disease , is a reversible condition where large vacuoles of triglyceride fat accumulate in liver cells via the process of steatosis...
s, hypertriglyceridemia
Hypertriglyceridemia
In medicine, hypertriglyceridemia denotes high blood levels of triglycerides, the most abundant fatty molecule in most organisms. It has been associated with atherosclerosis, even in the absence of hypercholesterolemia . It can also lead to pancreatitis in excessive concentrations In medicine,...
, severe insulin resistance
Insulin resistance
Insulin resistance is a physiological condition where the natural hormone insulin becomes less effective at lowering blood sugars. The resulting increase in blood glucose may raise levels outside the normal range and cause adverse health effects, depending on dietary conditions. Certain cell types...
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
Intron
An intron is any nucleotide sequence within a gene that is removed by RNA splicing to generate the final mature RNA product of a gene. The term intron refers to both the DNA sequence within a gene, and the corresponding sequence in RNA transcripts. Sequences that are joined together in the final...
ic single nucleotide polymorphism
Single nucleotide polymorphism
A single-nucleotide polymorphism is a DNA sequence variation occurring when a single nucleotide — A, T, C or G — in the genome differs between members of a biological species or paired chromosomes in an individual...
(C
Cytosine
Cytosine is one of the four main bases found in DNA and RNA, along with adenine, guanine, and thymine . It is a pyrimidine derivative, with a heterocyclic aromatic ring and two substituents attached . The nucleoside of cytosine is cytidine...
/T
Thymine
Thymine is one of the four nucleobases in the nucleic acid of DNA that are represented by the letters G–C–A–T. The others are adenine, guanine, and cytosine. Thymine is also known as 5-methyluracil, a pyrimidine nucleobase. As the name suggests, thymine may be derived by methylation of uracil at...
) 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
Fructose
Fructose, or fruit sugar, is a simple monosaccharide found in many plants. It is one of the three dietary monosaccharides, along with glucose and galactose, that are absorbed directly into the bloodstream during digestion. Fructose was discovered by French chemist Augustin-Pierre Dubrunfaut in 1847...
diets. This implies that a single nucleotide polymorphism can also modulate the sensitivity of a gene to dietary intervention.
Nutrigenetics and cardiovascular diseases
HyperlipidemiaHyperlipidemia
Hyperlipidemia, hyperlipoproteinemia, or hyperlipidaemia is the condition of abnormally elevated levels of any or all lipids and/or lipoproteins in the blood...
is usually associated with atherosclerosis
Atherosclerosis
Atherosclerosis is a condition in which an artery wall thickens as a result of the accumulation of fatty materials such as cholesterol...
and coronary heart disease
Coronary heart disease
Coronary artery disease is the end result of the accumulation of atheromatous plaques within the walls of the coronary arteries that supply the myocardium with oxygen and nutrients. It is sometimes also called 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
Apolipoprotein
Apolipoproteins are proteins that bind lipids to form lipoproteins and transport the lipids through the lymphatic and circulatory systems....
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 alleleAlleleAn allele is one of two or more forms of a gene or a genetic locus . "Allel" is an abbreviation of allelomorph. Sometimes, different alleles can result in different observable phenotypic traits, such as different pigmentation...
in the apolipoprotein EApolipoprotein EApolipoprotein E is a class of apolipoprotein found in the chylomicron and IDLs that binds to a specific receptor on liver cells and peripheral cells. It is essential for the normal catabolism of triglyceride-rich lipoprotein constituents.-Function:...
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 polymorphismSingle nucleotide polymorphismA single-nucleotide polymorphism is a DNA sequence variation occurring when a single nucleotide — A, T, C or G — in the genome differs between members of a biological species or paired chromosomes in an individual...
(-75 GGuanineGuanine is one of the four main nucleobases found in the nucleic acids DNA and RNA, the others being adenine, cytosine, and thymine . In DNA, guanine is paired with cytosine. With the formula C5H5N5O, guanine is a derivative of purine, consisting of a fused pyrimidine-imidazole ring system with...
/AAdenineAdenine is a nucleobase with a variety of roles in biochemistry including cellular respiration, in the form of both the energy-rich adenosine triphosphate and the cofactors nicotinamide adenine dinucleotide and flavin adenine dinucleotide , and protein synthesis, as a chemical component of DNA...
) in the apolipoproteinApolipoproteinApolipoproteins are proteins that bind lipids to form lipoproteins and transport the lipids through the lymphatic and circulatory systems....
A1 gene in women is associated with an increase in High density lipoproteinHigh density lipoproteinHigh-density lipoprotein is one of the five major groups of lipoproteins, which, in order of sizes, largest to smallest, are chylomicrons, VLDL, IDL, LDL, and HDL, which enable lipids like cholesterol and triglycerides to be transported within the water-based bloodstream...
-cholesterol levels with the increase in the dietary intake of polyunsaturated fatty acidPolyunsaturated fatty acidPolyunsaturated fatty acids are fatty acids that contain more than one double bond in their backbone. This class includes many important compounds, such as essential fatty acids and those that give drying oils their characteristic property....
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 polymorphismPolymorphism (biology)Polymorphism in biology occurs when two or more clearly different phenotypes exist in the same population of a species — in other words, the occurrence of more than one form or morph...
(-514 CCytosineCytosine is one of the four main bases found in DNA and RNA, along with adenine, guanine, and thymine . It is a pyrimidine derivative, with a heterocyclic aromatic ring and two substituents attached . The nucleoside of cytosine is cytidine...
C) in the hepatic lipaseLipaseA lipase is an enzyme that catalyzes the formation or cleavage of fats . Lipases are a subclass of the esterases.Lipases perform essential roles in the digestion, transport and processing of dietary lipids in most, if not all, living organisms...
gene is associated with an increase in protective HDL levels compared with the TThymineThymine is one of the four nucleobases in the nucleic acid of DNA that are represented by the letters G–C–A–T. The others are adenine, guanine, and cytosine. Thymine is also known as 5-methyluracil, a pyrimidine nucleobase. As the name suggests, thymine may be derived by methylation of uracil at...
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, gastric and breast cancerBreast cancer
Breast cancer is cancer originating from breast tissue, most commonly from the inner lining of milk ducts or the lobules that supply the ducts with milk. Cancers originating from ducts are known as ductal carcinomas; those originating from lobules are known as lobular carcinomas...
. Several gene variants have been identified as susceptibility genes. One example is the N-Acetyltransferase
N-Acetyltransferase
N-acetyltransferase is an enzyme that catalyzes the transfer of acetyl groups from acetyl-CoA to arylamines. They have wide specificity for aromatic amines, particularly serotonin, and can also catalyze acetyl transfer between arylamines without CoA. EC 2.3.1.5....
(NAT) gene. NAT is a phase II metabolism
Drug metabolism
Drug metabolism is the biochemical modification of pharmaceutical substances by living organisms, usually through specialized enzymatic systems. This is a form of xenobiotic metabolism. Drug metabolism often converts lipophilic chemical compounds into more readily excreted polar products...
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
Acetylation
Acetylation describes a reaction that introduces an acetyl functional group into a chemical compound...
s. NAT is involved in acetylation of heterocyclic aromatic amine
Aromatic amine
An aromatic amine is an amine with an aromatic substituent - that is -NH2, -NH- or nitrogen group attached to an aromatic hydrocarbon, whose structure usually contains one or more benzene rings. Aniline is the simplest example....
s found in heated products especially well cooked red meat. During cooking of muscle meat at high temperature, some amino acids may react with creatine
Creatine
Creatine is a nitrogenous organic acid that occurs naturally in vertebrates and helps to supply energy to all cells in the body, primarily muscle. This is achieved by increasing the formation of Adenosine triphosphate...
to give heterocyclic aromatic amines (HAA). HAA can be activated through acetylation to reactive metabolites which bind DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...
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.
Academic resources
- Public Health Nutrition, ISSN: 1475-2727 (electronic) 1368-9800 (paper)
See also
- GenomicsGenomicsGenomics is a discipline in genetics concerning the study of the genomes of organisms. The field includes intensive efforts to determine the entire DNA sequence of organisms and fine-scale genetic mapping efforts. The field also includes studies of intragenomic phenomena such as heterosis,...
- Orthomolecular medicineOrthomolecular medicineOrthomolecular medicine is a form of complementary and alternative medicine that seeks to maintain health and prevent or treat diseases by optimizing nutritional intake and/or prescribing supplements...
- Public health genomicsPublic Health GenomicsPublic Health Genomics is the use of genomics information to benefit public health. This is visualized as more effective personalized preventive care and disease treatments with better specificity, targeted to the genetic makeup of each patient...
- Roger J. WilliamsRoger J. WilliamsRoger John Williams , was an American biochemist who named folic acid and discovered pantothenic acid, and was a member of the National Academy of Sciences and President of the American Chemical Society....
http://nutritional-genomics.com