Speaking the language of life

Genomics is the branch of science and medicine that is concerned with the chemical and physiological interactions which underpin all cellular activities and their structural basis.

Over the past twenty years, numerous studies have been conducted to identify genetic variants (glitches) involved in the pathogenesis of Cardiovascular Diseases (CVDs) as well as other crucial aspects of health, fitness, nutrition and general wellness; these studies have been correlated to investigate the precise mechanism by which these glitches exert their effect on an individual.

Research
methodology

We investigated genetic markers by analyzing and reviewing existing markers in study articles across numerous databases, including genome-wide association studies (GWAS), meta-analyses, all databases in the National Center for Biotechnology Information (NCBI), medical subject headings (MeSH) in MEDLINE, and the Short Genetic Variations database (dbSNP). The Clinical Pharmacogenomics Implementation Consortium (CPIC) guidelines were used as the interpretation system for our drug responses report and the appropriate guideline measures were considered.

The initial search involved inputting gene names and/or the markers of interest across the above databases. Searches were conducted without language restrictions. The titles of articles found with these search criteria were scanned to eliminate those with a distinct dissociation with the condition or marker of interest.

Search entries in the GWAS catalogue resulted in articles that were selected based on their association count, reported trait, reported gene, and SNP number, with additional associated SNPs being shortlisted for later review and potential inclusion in the final report, depending on eligibility criteria. The reference lists of the selected studies were screened to obtain additional sources of studies for review.

A glimpse of our knowledge base

Knowledge is very important when it comes to medicine, health, diet and fitness.

Learning how you can work with your DNA rather than against it can help you make smarter choices in life.

NFIA-AS2

The NFIA-AS2 gene encodes a molecule that controls the expression of other genes by either switching them on or off. Some sources suggest the C variant of this gene is associated with the activation of erythropoiesis - the process of making red blood cells which carry oxygen to the muscles.

AMPD1

The variation in the gene AMPD1 has association with muscle recovery.

The AMPD1 gene codes for a protein which is found in muscles and plays a key role in energy metabolism. If this protein or the gene is reduced, then it can lead to exercise-induced myopathy, a condition where the muscle fibres lose their function.

LEPR

LEPR codes for a protein which binds leptin, a hormone found in fat cells with a key role in regulating body weight and fat metabolism. The protein is known as the leptin receptor. The interaction between leptin and the receptor is involved in the hunger/satiety response. Leptin interacts with areas of the brain to suppress hunger. The amount of leptin released correlates with the size of the fat cell. Therefore, the larger the cell, the greater the amount of leptin released.

The leptin receptor protein can be found on the surface of many different organs and tissues including the hypothalamus in the brain. The hypothalamus controls functions such as hunger, thirst, mood, sleep and our body temperature. The leptin receptor can only be activated when leptin attaches to it; they fit together much like a key in a lock. Once they are bound a series of chemical signals are triggered by the hypothalamus which if working correctly, affect hunger and should make you feel full.

Snacking behaviour is associated with obesity and is also linked to a variant on the genetic markers for the leptin receptor.

PCSK9

Proprotein Convertase Subtilisin/Kexin type 9 is encoded by PCSK9 gene on chromosome 1. Low density lipoproteins (LDL) are a primary carrier of cholesterol in the blood and are removed by liver LDL receptors. The PCSK9 protein controls the levels of LDL receptors on the liver cell membrane via intracellular enzymatic breakdown. This mechanism results in an indirect increase in LDL cholesterol. A specific mutation in the PCSK9 gene has been associated with an increased risk of developing a myocardial infarction.

CELSR2

The CELSR2 gene encodes the CELSR2 protein involved in cell communication. However, the specific function of this protein has not yet been determined. Polymorphisms in the gene have been shown to be associated with altered LDL levels.

MTHFR

Methylenetetrahydrofolate Reductase protein is encoded by the MTHFR gene on chromosome 1. The MTHFR protein is responsible for the metabolism of methionine (an essential amino acid) in cells. It plays a pivotal role in metabolism polymorphisms in this gene have been associated with a range of diseases from strokes, heart disease, and hypertension to neurological syndromes like Alzheimer's. The specific polymorphism that we test causes a decrease in the activity of the protein and a buildup of the methionine precursor homocysteine. Homocysteine can damage vascular walls and high levels are associated with the formation of blood clots. This additional hypercoagulability is especially pronounced when combined with other mutations like Factor V Leiden.

The MTHFR gene is also involved in the folate pathway. It codes for a protein needed to convert toxic compounds such as homocysteine (amino acid) into another compound known as methionine. If the variation of this gene is present, it cannot function as efficiently, causing toxic homocysteine to build up which can lead to coronary heart disease.

PROX1

PROX1 is a protein-coding gene which is involved in embryo development, specifically the heart, liver and pancreas. Mutation in the gene can predispose an individual to cardiac problems, blood and liver cancer and other types of conditions.

GALNT2

The GALNT2 gene codes for a protein which modifies the structure of other proteins by adding sugar molecules. This gene has been shown to influence triglyceride levels and diabetes.

 

Factor V (F5)

The genetic information for Coagulation Factor V (FV) is encoded by the F5 gene on chromosome 1. FV functions in the clotting cascade by binding to a key protein called thrombin to create a prothrombinase complex that helps create the web of proteins in the clot. Normally FV is broken down by bloodborne enzymes so it has a short half-life. However, a mutation called Factor V Leiden (FVL) makes the protein more resistant to breakdown. FVL stays active for much longer than normal FV and causes a hypercoagulable state where blood clots are more likely to form. This effect can be more pronounced in the presence of oral hormonal therapies.

 

MIA3

Melanoma Inhibitory Activity 3 protein or MIA3 gene is found on chromosome 1 and involved in transport within cells and Golgi apparatus organisation. A particular polymorphism on the MIA3 gene has been implicated in an increased risk of developing coronary artery disease and myocardial infarction.

NOS1AP

The genetic information for Nitric Oxide Synthase 1 Adaptor Protein is encoded by the NOS1AP gene on chromosome 1. In normal heart cells the protein works in heart cells to suppress calcium currents. A specific variation of the gene makes the NOS1AP protein more active and may prolong the QTc interval. This QT interval prolongation corresponds to the number of variant genes and can be significant when combined with verapamil therapy.

SORT1

The intergenic region located on chromosome 1p13 can present with a rs646776 mutation SNP allele. It is located next to the sortilin (SORT1) gene. It is partially responsible for regulating levels of progranulin (a cell growth and differentiation protein). Meta-analysis studies found associated with early-onset myocardial infarction.

ABCG8

The ABCG8 gene encodes a protein with a key role in promoting the excretion of cholesterol into the bile. Polymorphisms in the gene will alter the activity of the protein.

 

APOB

The APOB gene encodes the APOB protein, which is the main protein of LDLs. Alterations in this gene cause low levels of LDL (hypobetalipoproteinemia) and high cholesterol (hypercholesterolemia) due to a defect in the APOB protein.

 

GCKR

This gene codes for a protein with a crucial role in regulating glucose levels. Variants in this gene can lead to a loss of function, which in turn causes an increase in protein activity within the liver. This increase activates glucose metabolism and blocks the modification of fatty acids.

MCM6

MCM6 is a gene involved in the initiation of DNA replication – where a cell makes an identical copy of its DNA. Reduced activity in the LCT gene causes the occurrence of lactose intolerance in adults. The expression of the LCT gene is controlled by a DNA sequence known as a regulatory element. This element is located close to the MCM6 gene. Inherited changes in the regulatory element can cause the continued production of lactase in the small intestine. Therefore, this causes the individual to have a reduced ability to digest lactose as they age, causing the symptoms of lactose intolerance.

The variation (SNP) of this gene is most common in those of European background. For other backgrounds, other variations (SNPs) at other positions are likely to confer lactose tolerance. Environmental factors such as consuming dairy products throughout life may have an influence on whether lactose intolerance may occur or not (especially in the CT genotype).

 

G6PC2

The G6PC2 gene encodes a protein found in the pancreas that is involved in the release of glucose into the bloodstream. Alterations in this gene have been associated with Diabetes Mellitus type 2.

PPARG

PPARG is a protein-coding gene that is expressed in fat cells, a member of the peroxisome proliferator-activated receptor (PPAR) subfamily. The protein is involved in the regulation of fat and glucose metabolism. The gene allele alters the function of the protein which affects how fat and sugar are metabolised.

ADIPOQ

The ADIPOQ gene codes for a protein, called Adiponectin which is involved in the regulation of glucose levels and the breaking down of fats.The hormone is found in adipose tissue where it is involved in sensitizing the body to insulin. Obese people have been associated with significantly lower plasma adiponectin concentrations than non-obese subjects. 

 

SLC2A2

The SLC2A2 is a protein-coding gene that is involved in sensing blood glucose concentrations, also known as GLUT2 (facilitated glucose transporter member 2), and can determine individual’s sensitivity to sugar.

Individuals who display variants in this gene have shown an increased likelihood to eat foods containing high-sugar contents. Mutations can also impact the function of pancreatic beta cell development, which are important cells in the release of insulin and glucose regulation. Dysfunction of these cells can increase the risk of Diabetes Mellitus type 2.

 

ADCY5

ADCY5 gene enables protein synthesis for adenylate cyclase 5. The enzyme allows conversion of adenosine triphosphate (ATP) to cyclic adenosine monophospahte (cAMP), which stimulates insulin release. Alterations within this gene are associated with an increased chance of developing type 2 diabetes.

 

AGTR1

The genetic information for the Angiotensin II Receptor Type 1 protein is encoded on the AGTR1 gene on chromosome 3. Activation of the AGTR1 protein by angiotensin II causes the constriction of blood vessels and production of hormones to increase fluid and electrolyte retention in the kidneys. Two variations of this gene have been identified that through unknown mechanisms may decrease the efficacy of certain ACE inhibitors. By screening for these variations we can start to build a genetic score of ACE inhibitor efficacy in Coronary arterial disease called a PGX score.

 

MRAS

Muscle RAS Oncogene Homolog or MRAS gene is responsible for cell growth and differentiation. The encoded protein has been implicated in many proinflammatory and cancer pathways. A polymorphism in the MRAS gene has been associated with an increased risk of developing coronary artery disease.

NYP2R

The NYP2R gene codes for a protein that plays a key role in satiety signals and signalling involved in the brain's appetite response.

NPY is composed of 36 amino acids and is involved in several physiological and homeostatic processes in our central and peripheral nervous systems. NPY has been shown to interact with the appetite centre within the brain, increasing the feeling of hunger. This leads to increased food intake and subsequent weight gain.

ADH1B

ADH1B gene codes for a protein involved in the breakdown of alcohol in the liver. Alterations to this gene can make the protein less efficient at breaking down alcohol.

Populations with an East Asian background are more likely to present with an A allele, increasing their risk. However the A variant may have protective effects against upper gastrointestinal cancers.

 

GC

The gene, GC, encodes for the vitamin D-binding protein, found on numerous cells and acts as a docking station for vitamin D to bind and function. Gene variations can alter the function of the protein and alter vitamin D levels in the blood.

 

ACSL1

ACSL1 is a gene that codes for a protein required for the breakdown of fatty acids (building blocks of fat) in cells so energy can be released from them. The A allele of this gene is associated with lower V̇O2 max by an unknown mechanism.

 

PITX2

Paired Like Homeodomain 2 or PITX2 is a gene on chromosome 4 that encodes for a protein that initiates early stages of heart development.  A gene mutation is responsible for asymmetrical heart development and increases risk of atrial fibrillation development. Both copies of the defective gene are required to confer a genetic risk (homozygosity).

Not testing any genes here at the moment

PCSK1

The PCSK1 gene encodes the prohormone convertase 1/3 enzyme which is expressed in neuroendocrine cells (these are the cells which receive nervous messages stimulating an output/response). Prohormones are converted into functional hormones. Prohormone convertase 1/3 enzyme converts the prohormone into a functioning hormone associated with the metabolism of energy.

An analysis of 13000 individuals found a significant association of a single nucleotide polymorphism (variation) in the PCSK1 gene with the increased risk of obesity. The gene has also been associated with childhood obesity.

The polymorphism has also shown interaction with age on the level of obesity and BMI. For example, the variation (Single Nucleotide Polymorphism) was linked to obesity in those under the age of 59 rather than older individuals.

Therefore, by determining your genotype associated with the PCSK1, your phenotype will also be determined. The phenotype will tell you how your energy metabolism is functioning.

HMGCR

The HMGCR gene encodes a protein that is suppressed by cholesterol. The cholesterol that suppresses the coded protein is derived from the breakdown of LDL. A variation in the HMGCR gene has been associated with increased LDL cholesterol in multiple populations.

 

APC

Adenomatous Polyposis Coli or APC gene is located on chromosome 5. It is involved in cell adhesion, development and interactions. The role of APC as a tumor suppressor has long been known, recent studies have shown a male-specific association between an APC polymorphism and an increased risk of developing coronary artery disease.

EDN1

EDN1 or endothelin 1 is a key regulator of blood pressure. Exercise increases shear stress and so leads to lower production and release of EDN1, resulting in lower blood pressure.

The peptide also has other roles which include the stimulation and release of hormones, cell division and regulation of the central nervous system.

 

TNF

TNF gene is associated with muscle repair. The gene can determine how the combination of C-reactive protein (CRP), a substance produced by the liver in response to inflammation and eNOS affect muscle repair. If there is a lot of CRP in circulation, this can indicate that there is inflammation present which can be caused by various conditions including damage to muscles. eNOS, on the other hand, is a signalling molecule which regulates blood flow, including the supply of blood to our muscles.

PHACTR1

Phosphatase and Actin Regulator 1 is encoded by PHACTR1 gene on chromosome 6. The protein is an inhibitor of Protein Phosphatase 1 and binds to actin. It has a role in regulating the skeletal structure of cells. PHACTR1 is involved in the functioning of endothelial (vascular) cells and in the formation of atherosclerotic plaques. A variation of this gene has been associated with coronary artery disease and early-onset myocardial infarction.

MTHFD1L

Methylenetetrahydrofolate Dehydrogenase 1 Like protein or MTHFD1L gene is responsible for  the metabolism of different nucleic acids, amino acids, and folate in cells. Multiple studies have shown that a polymorphism of this gene is associated with a more severe prognosis after an acute coronary artery event.

IL-6

IL-6 determines protein levels of interleukin-6 and its role in muscle growth and muscle regeneration. IL-6 has a key role in inflammation and cell development. Muscle cells produce the largest amount of IL-6 after exercise compared to other cells.

The coded protein also has growth factor abilities and is produced in skeletal muscle following an exercise response.

The gene allele has been shown to have some relation to diabetes mellitus type 2 and prostate cancer. The presence of the G type of the IL-6 gene is common in elite athletes, due to the regular muscle contraction and subsequent production of IL-6. The other C allele is associated with increased muscle damage in non-athletes.

GCK

GCK is a protein-coding gene that initiates the uptake of glucose by beta-cells in the pancreas and in the liver at normal glucose concentrations. Alterations in this gene have been associated with Diabetes Mellitus type 2.

Intergenic (DGKB/TMEM195)

DGKB/TMEM195, this gene codes for proteins which play a key role in cellular processes. This gene is associated with pancreatic beta cell function.

NOS3

The nitric oxide synthase three (NOS3) gene codes for a protein which is involved in the production of nitric oxide, a free radical, involved in many biological processes including the relaxation of muscles. It is particularly associated with smooth muscle especially vascular muscles. Variations within this gene can affect the availability of nitric oxide. For example, women with the TT genotype have been shown to have gained greater strength than those with the G form of the gene.

MLXIPL

This gene codes for a protein which binds and activates carbohydrate proteins that are responsible for initiating the breakdown of triglycerides. Mutations in this gene have been linked to reduced HDL-cholesterol levels and increased triglyceride levels.

NAT2

NAT2 is a protein-coding gene that is involved in molecular modification. Although the mechanism is unclear, polymorphisms in this gene alter insulin sensitivity, altered glucose uptake, insulin sensitivity, lipolysis and adipocyte differentiation.

 

LPL

Lipoprotein Lipase or LPL gene is located on chromosome 8 and has a role to break down bloodborne triglycerides for cell utilisation. LPL is involved in promoting cellular uptake of chylomicron remnants and free fatty acids. A polymorphism of the LPL gene provides a protective benefit on carriers, resulting in a reduced risk of developing coronary artery disease.

LPL is a gene that encodes a protein responsible for breaking down the fats in lipoproteins, which enables the cells to take up free fatty acids and other proteins. Variants in this gene have been previously associated with levels of high triglycerides and low of HDL levels.

 

XKR6

The XKR6 gene is mainly expressed in the frontal cortex and seems to have a role in the nervous system. Although the mechanism is not clear, polymorphisms in this gene have been shown to increase triglyceride levels.

SLC30A8

SLC30A8 gene codes for a protein that is involved in transporting zinc in the pancreas as well as playing a key role in the secretion of insulin.

 

TRIB1

This gene encodes a protein involved in the production of fats that can be used as energy storage compartments. Polymorphisms in this gene can contribute to changes in triglyceride levels.

GLIS3

GLIS3 is a protein-coding gene in the development of pancreatic beta cells. Alterations in this gene have been associated with Diabetes Mellitus type 2.

TTC39B

The TTC39B gene encodes a protein whose function has not yet been determined. Speculation, based on its similarity to proteins in other organisms, suggests the protein acts as part of a group thought to be necessary for the function of the liquid compartments within cells; which recognise and break down molecules containing genetic information. The G allele in the SNP found in this gene, which lowers TTC39B levels, is also associated with decreased HDL-cholesterol levels.

 

CDKN2B

Cyclin Dependent Kinase Inhibitor 2B protein or CDKN2B gene is located on chromosome 9 and acts as a cell growth regulator. Multiple studies have corroborated an association between a CDKN2B polymorphism and an increased risk of developing coronary artery disease.

Intergenic 9p21

 The intergenic region located on chromosome 9p21 can present with a rs10757278 mutation SNP allele. It is located next to a cell cycle gene (CDKN2A). A number of studies have suggested a relation between the 9p21 sequence and its relation to coronary artery disease, aortic aneurysm, and stroke. Studies have found a variation of the 21q22 sequence to be associated with early-onset myocardial infarction.

COL5A1

The COL5A1 gene enables production of type V collagen. Collagen is a structural protein needed to strengthen various tissues in the body including muscles, bones and tendons.

There are variations in this gene as well. The presence of the T allele is linked with an increased chance of developing achilles tendinopathy.

A combination of the G allele in the MMP3 gene and the T allele in the COL5A1 gene significantly increases the chance of achilles tendinopathy.

 

ABCA1

The ABCA1 gene codes for a protein involved in the removal of lipids from the system with the help of cholesterol. Mutations in this gene have been associated with HDL deficiency.

Not testing any genes here at the moment

ADRA2A

ADRA2A is a protein-coding gene that moderates the release of insulin. Alterations in this gene have been associated with Diabetes Mellitus type 2.

 

TCF7L2

TCF7L2 gene codes for a protein that plays a key role in regulating pancreatic beta-cell function.

 

GRK5

The genetic information for G Protein-Coupled Receptor Kinase 5 is encoded by the GRK5 gene on chromosome 10. The GRK5 protein augments the activity of receptors on the surface of cells (eg. Beta adrenergic receptors). It is found all around the body, but is abundant in muscle and heart cells where it has been shown to play a role in development. Levels of GRK5 in heart cells have been correlated with a protective effect in heart failure. A polymorphism on the GRK5 gene changing a glutamine at position 41 to a leucine enhances the activity of the protein resulting a relative genetic blockade of beta receptors and facilitating the effects of beta blocker therapy.

 

ADRB1

The genetic information for the Beta 1 Adrenergic Receptor is encoded by the ADRB1 gene on chromosome 10. Beta 1 adrenergic receptors are primarily found on the surface of certain kidney and heart cells. A mutation at position 389 changing a glycine amino acid to an arginine alters the beta blocker binding site. This ADRB1 variant binds more strongly with beta blockers. Carrying two of these variant genes has been associated with a better response to beta blocker therapy in heart failure in terms of mortality and LVEF.

 

CYP2C9

The genetic information for the Cytochrome p450 2C9 enzyme is encoded on the CYP2C9 gene on chromosome 10. This enzyme normally functions in the liver to break down a range of compounds including warfarin. Some mutations of the CYP2C9 gene can result in an enzyme that does not function as well to break down warfarin. The type and number of these mutations can result in progressively slower metabolism of warfarin and may indicate the need for a lower dose.

 

CYP2C19

The CYP2C19 gene on chromosome 10 holds the genetic information for the Cytochrome 2C19 enzyme. The CYP2C19 enzyme in the liver is instrumental in converting clopidogrel into its active form. There are many variations that can cause a clinically significant decrease in the activity of the enzyme. One variant actually increases activity by boosting expression of the gene, so there is more CYP2C19 and activated clopidogrel available during therapy. By screening for these variants it is possible to compare genotype results to clinical guidelines and improve the results of clopidogrel therapy.

 

CXCL12

C-X-C Motif Chemokine 12 is a chemokine protein found on chromosome 10. The cytokines activates leukocytes in the immune system and triggered by proinflammatory stimuli. A polymorphism on the CXCL12 gene has been implicated in an increased risk of developing coronary artery disease and myocardial infarction.

MADD

The MADD gene codes for a protein which is involved in numerous pathways including the secretion of insulin. The deletion and variants within this gene are associated with an increased chance of developing Diabetes Mellitus type 2.

 

Factor 2 (F2)

The genetic information for Prothrombin is encoded by the Factor 2 gene on chromosome 11. Prothrombin functions in the clotting cascade by being cleaved into thrombin and having its activity enhanced by FV and forming a prothrombinase complex. The complex uses a protein called actin to create a web of filaments that form a large part of a blood clot. A certain mutation in the F2 gene causes levels and activity of prothrombin in the blood to be much higher than normal. This results in a hypercoagulable state where blood clots are more likely to form.

 

HBB

The genetic information for hemoglobin beta protein is encoded on the HBB gene on chromosome 11. A mutation in the gene results in a change in one of the amino acids in the protein. This new amino acid is hydrophobic and prefers to stick to nearby hemoglobin proteins. A single copy of the mutant gene can usually be balanced by the normal HBB protein and rarely results in sickle cell anaemia. Generally, 2 copies of the polymorphism are necessary to cause sickle cell anaemia.

TCN1

TCN1 is a protein-coding gene that binds to vitamin B12 to aid its absorption. Gene variations are associated with altered vitamin B12 levels.

 

ACTN3

Actinin Alpha 3 is a protein-coding gene. It encodes for a protein which is expressed in muscles and found in fast twitch muscle fibres, playing a key role in coordinating muscle fibre contractions.

The ACTN3 gene is associated with elite athletic performance. The two variant forms of the gene, also known as alleles, are T and C. The T allele codes for a non-functioning protein which means the fast twitch muscle fibres have a reduced function. In the genotypes with the C allele, CC or CT, individuals will produce the functional protein. These genotypes are more common in elite athletes.

 

MMP3

The MMP3 is a protein-coding gene that belongs to the the matrix metalloproteinase family (MMP). The MMP proteins are involved in degrading structural proteins such as cartilage, fibronectin, collagen and laminin. These are needed for the structural components of the human body such as bones, muscles, cells, hair, skin and nails.

There are variations of this gene. For example, the presence of the G variant increases the expression of MMP3. Also, a combination of the G allele in the MMP3 gene and the T allele in the COL5A1 gene significantly increases the chance of achilles tendinopathy.

 

DRD2

DRD2 (dopamine receptor D2) codes for a protein that binds to dopamine in the brain. Dopamine is involved in the feeling of pleasure we get when we eat as well as other addictive behaviour pathways. Therefore, alterations to this gene can affect our food pleasure response. The altered expression of DRD2 is often shown in people who are obese or in those addicted to drugs. Although the process of homeostasis largely controls the regulation of body weight, our motivation for food is associated with reward. The D2 receptor genes and its variants have been associated with enhanced dopamine neurotransmission, a factor which is significantly related to binge eating disorders. Predisposition to this disorder can increase the risk of weight gain.

 

MTNR1B

MTNR1Bgene codes for a protein which has key roles in insulin secretion and glucose production. The gene is expressed in numerous cells including the pancreatic beta cells where the protein coded by this gene is secreted.

 

FADS1

FADS1 is a gene that encodes the FADS1 protein which regulates the breakdown of fatty acids. Polymorphisms of the FADS gene have shown, on average, an association with decreased HDL cholesterol levels.

 

ZNF259

The ZNF259 gene (now known as the ZPR1 gene) codes for a protein that interacts with other proteins associated with motor neurons. These proteins edit molecules containing genetic information. Polymorphisms in this gene can contribute to changes in triglyceride levels as the G allele for a SNP variant on this gene is also associated with lower levels of HDL.

SLCO1B1

The genetic information for the Organic Anion-Transporting Polypeptide 1B1 protein is encoded by the SLCO1B1 gene on chromosome 12. In liver cells the SLCO1B1 protein transports a number of molecules from the bloodstream. Statins are used to reduce blood cholesterol by acting on liver cells. A variant of the SLCO1B1 gene can result in reduced protein reaching the outer wall of liver cells. The variant can result in increased statin levels and increased risk for myopathy.

 

BCAT1

The genetic information for Branched Chain Amino Acid Transferase 1 is encoded by the BCAT1 gene on chromosome 12. The BCAT1 protein works to catalyse a metabolic process that generates amino acids necessary for cell growth from precursor molecules. The polymorphism tested for in this gene has been associated with an increased risk of developing hypertension.

KCTD10

KCTD10 codes for a protein involved in DNA production and cell division. Recent studies have associated a single nucleotide polymorphism (SNP), a small change in KCTD10, with a decrease in plasma HDL levels.

 

HNF1A

This gene codes for a protein which regulates the activity of numerous other genes that are involved in blood coagulation and LDL transport. Individuals with variants of this gene have an increased chance of both primary and recurrent coronary artery disease events, as well as an enhanced clinical benefit from statin therapy.

Not testing any genes here at the moment

Not testing any genes here at the moment

Not testing any genes here at the moment

BDKRB1

The genetic information for the Bradykinin Receptor B1 protein is encoded on the BDKRB1 gene on chromosome 14. Activation of the BDKRB1 protein by bradykinin can cause a variety of inflammatory or stress responses. A variation of this gene has been identified that through unknown mechanisms may decrease the efficacy of certain ACE inhibitors. By screening for this variation we can start to build a genetic score of ACE inhibitor efficacy in CAD called a PGX score.

Not testing any genes here at the moment

NMB

Neuromedin beta (NMB) is an obesity candidate gene. It is a member of the bombesin-like protein family which has several biological effects associated with eating behaviours and obesity. The NMB gene codes for the protein NMB which plays a key role in regulating dietary intake and energy balance by negatively directing eating behaviour.

Studies have found that a mutation of the NMB can lead to susceptibility to hunger, disinhibition and increased body weight. Low levels of NMB can leave individuals genetically susceptible to obesity.

 

CYP1A2

Caffeine is metabolised in the liver by the protein cytochrome P450, which is encoded by the gene CYP1A2. This protein is responsible for breaking down 95% of caffeine before it can be safely removed from our system by the kidneys. Variations in the gene can alter its action which can affect the rate in which caffeine is broken down.

 

CYP1A2 may have some effects upon metabolism of other drugs, given that cytochrome P450 is involved in the breakdown of various compounds.

 

LIPC

The LIPC gene encodes a protein that helps to keep lipoproteins in balance, by regulating the formation of LDL and the transport of HDLs. One polymorphism in the LIPC gene has been associated with increased HDL cholesterol. Studies have suggested ethnic variation between LIPC levels post-exercise.

 

SMAD3

SMAD Family Member 3 protein or SMAD3 gene is found on chromosome 15. It is a signal transducers and gene activity modulators that mediate multiple signally pathways, initiated by TGF-β. Several studies have associated a particular polymorphism in SMAD3 with an increased risk of developing coronary artery disease.

 

CHRNA3

The CHRNA3 gene Neuronal acetylcholine receptor subunit alpha-3 encodes the information for a member of the nicotinic acetylcholine receptor family of proteins. These proteins are ion channels that play a role in neurotransmission in the brain. Studies have associated a specific mutation of the protein with increased susceptibility to nicotine dependence (smoking), lung cancer, and the likelihood of developing peripheral artery disease.

SH2B1

The SH2B1 gene codes for the SH2B adapter protein. It interacts with the insulin receptor, with leptin signalling during fat metabolism. SH2B1 allows the binding of leptin to its receptor enabling insulin and leptin signalling.

Variations in or around the SH2B1 gene have a strong association with obesity which has been shown in 2 large genome studies focussing on body mass index (BMI). Early onset obesity is also associated with deletions of SH2B1.

VKORC1

The genetic information for the Vitamin K Epoxide Reductase Complex 1 protein is encoded on the VKORC1 gene on chromosome 16. Normally the protein metabolises vitamin K for incorporation into clotting factors. A polymorphism on the gene produces a protein that is not as effective. Functionally this facilitates the anti-clotting action of warfarin and may indicate a need for a lower dose.

BCMO1

BCMO1 is a protein-coding gene that is involved in the conversion of provitamin A (β-carotene) into vitamin A (retinol) within the small intestine. Carotene is a compound associated with Vitamin A and play an important role in our immune system and work to maintain or improve our vision. Variations in this gene reduce the activity of BCMO1, resulting in higher levels of unconverted β-carotene.

 

FTO

FTO is known as the fat mass and obesity associated gene. Variations of the gene been associated with the development of type II diabetes. Many studies have found association between FTO variations and a higher BMI.

A variation in the FTO gene increases the blood hormone levels of ghrelin (hunger hormone), increasing the risk of obesity. Individuals have an increased appetite and feel hungry soon after eating a meal. In addition, it has been shown individuals tend to prefer high-calorie foods even before they become overweight.

 

CETP

The CETP gene is a protein-coding gene; the protein encoded by this gene is involved in transporting HDL to other proteins. Defects in this gene are a cause of hyperalphalipoproteinemia 1 and high HDL cholesterol levels.

 

LCAT

The LCAT gene encodes a protein involved in transporting cholesterol out of the blood and tissues. The cholesterol is transported to the liver and redistributed or removed from the body. A polymorphism in this gene has been associated with increased HDL levels.

 

CDH13

Cadherin 13 or CHD13 gene codes for a membrane protein of endothelial cells lining blood vessels. The protein protects the cells from oxidative stress and programmed cell death (apoptosis), thus is associated with resistance to atherosclerosis. Variations of the gene can result in a defective protein with a reduced protective factor. Mutations in the gene have been associated with endothelial cell damage and an increased risk of developing coronary artery disease.

ASGR1 (Gene X)

The ASGR1 gene codes for a protein subunit of the asialoglycoprotein receptors, which are located on the surface of the liver and bind glycoproteins. These receptors transport glycoproteins from the circulation into cells. The genetic variation of ASGR1, dubbed Gene X, has been associated with a 34% reduction in the risk of developing coronary artery disease. It also leads to decreased levels of LDL cholesterol. This constitutes one of the largest cardioprotective links to any heart condition to date. An effect that is present when one or both copies of a gene called ASGR1 are dysfunctional and produce a short-lived version of the protein.

Not testing any genes here at the moment

Not testing any genes here at the moment

MC4R

The MC4R gene codes for the melanocortin four receptor, which is found in the hypothalamus of the brain. Sensors identify high energy levels or food consumption has taken place, therefore signally satiety signals. The signals activate our nerve cells via the melanocortin four receptors, alerting us that we feel full. Moreover, when energy levels are low, the hunger response is triggered.

If mutations are present in the MC4R gene, it can lead to obesity. A common variant in this gene causes the MC4R protein level to be reduced in the hypothalamus and is carried by around 22% of the population. The individuals with this variant experience an increase in their appetite and don’t always feel full, so they snack more and eat larger meals which tend to have a high-fat content.

MC4R is associated with monogenic obesity (rare, severe early onset and presenting with other endocrine disorders). Individuals identified with MC4R monogenic conditions respond well to low-calorie diets as well as multidisciplinary interventions including exercise and behaviour/nutritional therapy.

 

LIPG

The LIPG gene encodes a protein involved in lipoprotein breakdown. The polymorphism in the LIPG gene is associated with increased HDL cholesterol.

ANGPTL4

The ANGPTL4 gene encodes a protein which regulates glucose levels. It is also involved in sensing insulin and breaking down fats. The T allele of the gene has shown associations with increased HDL cholesterol.

 

LDLR

This gene provides the instructions for producing the low-density lipoprotein protein receptor (LDLR). The receptor binds to the LDL particles, the primary carriers of cholesterol in the blood, it is degraded, and cholesterol is made available as a result. Polymorphisms in this gene have been shown to influence LDL levels.

 

NCAN

The NCAN gene encodes a protein involved in regulating cell clumping and migration. Variations (polymorphisms) in this gene can contribute to changes in triglyceride levels. Researchers identified the T allele of the SNP to be associated with increased LDL cholesterol.

 

CACNA1

The alpha 1c subunit of the L-type calcium channel is the primary pore forming unit, the binding site for beta blockers, and is encoded by the CACNA1 gene on chromosome 1. Two variations of the CACNA1 gene can change CCB interaction. The result is one protein with a positive response to verapamil therapy and another that is associated with a positive response to beta-blocker therapy. By screening for these variations we can determine if verapamil or beta-blockers might have a more positive effect if used as therapy for hypertension and stable coronary artery disease.

FUT2

FUT2 is protein-coding gene that is involved in the modification of carbohydrates that are associated with B12 absorption. Gene variations are associated with altered vitamin B12 levels.

APOE

Apolipoprotein E or APOE gene encodes a protein that form lipoproteins, which are transported in the lymphatic and circulatory system. APOE is the principle cholesterol carrier in the brain and is involved in fat metabolism. There are three main variants (E2, E3, and E4) that occur at two different sites. E3 and E4 are considered normal variations of the gene and do not increase the risk of developing Type III Hyperlipoproteinemia (HLP). The E2 apoprotein variant binds poorly to cell surface receptors and is associated with slow metabolism of fat. Type III HLP is an autosomal recessive condition. This means both copies of E2 (homozygosity) to put you at risk of the condition.

Not testing any genes here at the moment

HNF4A

The HNF4A gene codes for a protein which regulates the activity of several genes involved in blood clotting and LDL transport. The change in this gene has been associated with decreased HDL cholesterol.

 

PLTP

PLTP gene codes for a protein mainly expressed in the liver and is responsible for the transfer of fats from very low-density lipoproteins (VLDL) to high-density lipoprotein (HDL). Variations in this gene can contribute to changes in triglyceride levels.

 

MAFB

The MAFB gene encodes a protein with an important role in regulating the formation of blood cells. Studies have demonstrated polymorphisms in the MAFB gene to be associated with increased LDL cholesterol.

Not testing any genes here at the moment

Intergenic 21q22

The intergenic region located on chromosome 21q22 can present with a rs9982601 mutation SNP allele.  It is located next to a potassium channel gene (KCNE2). Studies have found a variation of the 21q22 sequence to be associated with early-onset myocardial infarction.

Not testing any genes here at the moment

PPARA

Peroxisome proliferator-activated receptor alpha is a protein-coding gene, involved in the regulation of fats (lipids) in the liver. A variant of the PPARA gene, G, is believed to change lipid metabolism and is associated with the individual having a higher frequency of slow twitch muscle fibres, essential for endurance training.

 

CYP2D6

The genetic information for the Cytochrome p450 2D6 enzyme is encoded on the CYP2D6 gene on chromosome 22. This enzyme is found primarily in the liver and responsible for 60% of metoprolol breakdown. A large number of polymorphisms on the gene can reduce the functioning of the enzyme. By screening for the known variations of the CYP2D6 gene, their cumulative effect can be calculated. Individualised metoprolol therapy can be prescribed based on the CYP2D6 activity.

Not testing any genes here at the moment

AGTR2

AGTR2, is located on the X chromosome, band Xq22-q23, codes for angiotensin II receptor type 2, which has an important role in skeletal muscle development and metabolism. The A allele is more common in power athletes, as it is associated with a higher number of fast twitch muscle fibres. The C allele is more common in endurance athletes, as it is associated with a higher number of slow twitch muscle fibres and a higher V̇O2 max (the highest rate possible for your body to transport oxygen to muscles so they can produce energy).

Not testing any genes here at the moment

Not testing any genes here at the moment

Quality Assurance

To sustain an effective quality assurance plan we have developed, in conjunction with staff, management and clients, a procedure explained in a variety of different policies, service agreements and codes of practice, with the objective of eliminating errors and deficiencies.

We are partnered with accredited laboratories in the UK and US who are compliant with the relevant CLIA, CAP and ISO "International Organization for Standardization" standards (ISO 15189 and ISO 17025) and have put in place specific service agreements that detail the necessary quality assurances required to supply their services to us.

Additionally, Rightangled’s partnership scheme with healthcare professionals enables us to provide relevant medical and wellness assessments at the end of each test analysis. Such reporting is based on genetic and self-reported lifestyle risk factors for more comprehensive assessment with an actionable plan on what the end-user can do next.

Our service is supported by a wide range of scientific journals, healthcare industry providers, and the great reviews of our clients. We are backed by NHS England, regulated by the CQC, registered with the Information Commissioner's Office “ICO” and fully compliant with GDPR.