Enzymes are chemicals made inside the body. They are involved in important chemical reactions, including digesting food and breaking down medicines and poisons. Enzymes can be made by human cells because the genes there include coded instructions (in the DNA) on how to make them. Although each gene is the same in most people, there are slight differences that are unique to each individual. Amongst these differences in people’s genes, there are some common variations (affecting around 1 in 10 people or more). These common differences between individuals’ genes may affect the activity of the different enzymes produced inside the body.
Eurogene can advise better about what a person should eat by testing some of these genes. The advice depends on the individual’s genetic make-up. Some information about the 19 genes that Eurogene tests, is given below.
Six detoxification genes (including CYP, NAT and GSTgenes)
Some people remove chemicals that are harmful to the body more quickly than others. By understanding the variations of genes that affect the ability to detoxify, we can improve a person’s health by recommending specific fruits and vegetables that will help the body remove toxins. For example, cruciferous vegetables such as broccoli are useful in helping to remove toxins for people with specific genetic variations. Recommendations could also include altering food preparation methods to reduce the intake of toxins. Eurogene screens for six genes that have an influence on detoxification processes within the body.
CYP, NAT and GST enzymes (genes) are part of the body’s defenses against cancer and other diseases caused by toxic chemicals. Cytochrome P450 (CYP) enzymes are chemicals involved in the metabolism, or chemical breakdown, of many substances in the body - including vitamins, fatty acids, drugs, pesticides and carcinogens (cancer-causing substances). The NAT enzyme helps the body remove cancer-causing chemicals called “heterocyclic aromatic amines” that are found in cured and smoked meat and meat cooked quickly at high temperatures. GST enzymes also play a part in the defense against harmful chemicals – they react chemically with the poisons after they have been broken down and help change them to a form that can be excreted from the body.
There are 58 known CYP genes and at least 22 GST genes. Some of them have many different forms – for example, 80 different forms of the gene CYP2D6 have been discovered so far. Most of the variations are rare but some are more common. There are also fairly common variations in the GST genes GSTM, GSTT1 and GSTP1, which affect the activity of the enzymes being made inside the cells. There are two known NAT genes, NAT1 and NAT2 that also have common variations. Differences in the CYP, NAT and GST genes can affect how well the body deals with cancer-causing chemicals. Pollutants such as cigarette smoke can increase the activity of the CYP1A1 enzyme, as can protective foods such as brassica vegetables (e.g. cauliflower, Brussels sprouts and broccoli). Cruciferous vegetables (which include brassicas) and garlic are also known to influence the activity of other CYP enzymes.
One anti-oxidant gene (MnSOD)
For some people a normal diet provides all the antioxidants they need to stay healthy. Others, with particular genetic variations, may require additional anti-oxidants in their diet to effectively control free radicals. Eurogene’s antioxidant screen focuses on a gene that is influential in the removal of free-radicals. MnSOD is one of three known enzymes in the body that help breakdown toxic “oxygen free radicals” and is involved in detoxification.
One tissue repair gene (MTHFR)
Eurogene also deals with the tissue repair gene MTHFR because certain vitamins are essential for maintaining healthy tissues in many parts of the body. Our bodies produce many of these vitamins internally but some have to be obtained through our diet. We screen for a gene which influences how the body absorbs Vitamin B6, Vitamin B12 and folic acid. These vitamins have to be obtained from the diet or additives. The correct quantity of these vitamins is important for health and Eurogene can identify individuals who need to boost their intake of these vitamins to ensure effective tissue repair. For people with these variations, anti-oxidant supplements in the form of specific fruits and vegetables or vitamins are recommended to maintain health and well-being. Specific dosage recommendations are made depending on the genetic profile revealed.
MTHFR is an enzyme involved in producing a form of folate (a vitamin) that plays a part in lowering the levels of a chemical called homocysteine in the body. Too little folate, or too much homocysteine, have been linked with many health problems. There is a common form of the MTHFR gene which reduces the activity of the MTHFR enzyme. Lack of folate in early pregnancy has been linked to birth defects and high levels of homocysteine (Hcy) have been linked to heart disease and strokes. It has also been suggested that low levels of folate can cause cancer (particularly bowel cancer) and mental illnesses such as Alzheimer’s disease and Dementia. Studies have found a link between the less active form of MTHFR and high levels of Hcy – but if someone has sufficient (average or above) levels of folate in his diet, the form of the gene he has does not seem to matter. On the other hand, if someone has below average folate levels and are male or a post-menopausal woman, having the less active form of the gene may make his folate deficiency worse. Low folate levels in pregnant women have been associated with birth defects known as neural tube defects (which include spina bifida) in babies. This is why women are often advised to take supplements of folic acid before conception and during early pregnancy.
One alcohol consumption gene (ALDH2)
Alcohol has no direct nutritional content and by-products formed when the body processes alcohol can be harmful to the body. Eurogene screens for a gene that affects how the body copes with alcohol consumption. For individuals with a specific genetic variation, Eurogene recommends that they avoid alcohol to improve health and well-being.
The ALDH2 enzyme is found mainly in the liver and helps the body deal with alcohol by breaking down a chemical called aldehyde. The ALDH2 enzyme can be inactive in some people with a particular form of the ALDH2 gene – this form of the gene is quite common in Asian people. The ALDH2 gene can be more important than other factors in how the body deals with alcohol because one form of the gene can make the enzyme almost completely inactive. This means that people with this gene get drunk easily because of the build up of acetaldehyde in the body – often becoming flushed, dizzy and sick. People with this form of the gene who do drink alcohol also seem to be at a higher risk from many cancers. Eurogene advise you not to drink alcohol if you have this gene.
MS-MTRR gene – the methylation gene
The MTRR gene encodes methionine synthase reductase. Methionine is an essential amino acid in mammals. It is required for protein synthesis and is a central player in 1-carbon metabolism. In its activated form, S-adenosylmethionine (SAM), it is the methyl donor in hundreds of biologic transmethylation reactions and the donor of propylamine in polyamine synthesis. The eventual product of the demethylation of methionine is homocysteine, and its remethylation is catalyzed by a cobalamin-dependent enzyme, methionine synthase. Over time, the cob(I)alamin cofactor of methionine synthase becomes oxidized to cob(II)alamin, rendering the MTR enzyme inactive. Regeneration of functional enzyme requires reductive methylation via a reaction catalyzed by MTRR in which SAM is used as a methyl donor.
CBS – the homocystinouria gene
The protein encoded by this gene is involved in the transsulfuration pathway. The first step of this pathway, from homocysteine to cystathionine, is catalyzed by this protein. CBS deficiency can cause homocystinuria which affects many organs and tissues, including the eyes and the skeletal, vascular and central nervous systems.
APOC3, LPL – the lipid genes
Apolipoprotein C-III is a very low density lipoprotein (VLDL) protein. APOC3 inhibits lipoprotein lipase and hepatic lipase; it is thought to delay catabolism of triglyceride-rich particles. The APOA1, APOC3 and APOA4 genes are closely linked in both rat and human genomes. The A-I and A-IV genes are transcribed from the same strand, while the A-1 and C-III genes are convergently transcribed. An increase in apoC-III levels induces the development of hypertriglyceridemia. LPL encodes lipoprotein lipase, which is expressed in heart, muscle, and adipose tissue. LPL functions as a homodimer, and has the dual functions of triglyceride hydrolase and ligand/bridging factor for receptor-mediated lipoprotein uptake. Severe mutations that cause LPL deficiency result in type I hyperlipoproteinemia, while less extreme mutations in LPL are linked to many disorders of lipoprotein metabolism.
CETP – the atherosclerosis gene
Cholestery ester transfer protein (CETP) transfers cholesteryl esters between lipoproteins. CETP affects susceptibility to atherosclerosis.
ACE – the blood pressure gene
This gene encodes an enzyme involved in catalyzing the conversion of angiotensin I into a physiologically active peptide angiotensin II. Angiotensin II is a potent vasopressor and aldosterone-stimulating peptide that controls blood pressure and fluid-electrolyte balance. This enzyme plays a key role in the renin-angiotensin system. Many studies have associated the presence or absence of a 287 bp Alu repeat element in this gene with the levels of circulating enzyme or cardiovascular pathophysiologies.
VDR the metabolic gene
This gene encodes the nuclear hormone receptor for vitamin D3. This receptor also functions as a receptor for the secondary bile acid lithocholic acid. The receptor belongs to the family of trans-acting transcriptional regulatory factors and shows sequence similarity to the steroid and thyroid hormone receptors. Downstream targets of this nuclear hormone receptor are principally involved in mineral metabolism though the receptor regulates a variety of other metabolic pathways, such as those involved in the immune response and cancer. Mutations in this gene are associated with type II vitamin D-resistant rickets.
COL1A1 – the osteoporosis gene
This gene encodes the major component of type I collagen, the fibrillar collagen found in most connective tissues, and the only component of the collagen found in cartilage. Mutations in this gene are associated with osteogenesis imperfecta, Ehlers-Danlos syndrome, and idiopathic osteoporosis. Reciprocal translocations between chromosomes 17 and 22, where this gene and the gene for platelet-derived growth factor beta are located, are associated with a particular type of skin tumor called dermatofibrosarcoma protuberans, resulting from unregulated expression of the growth factor.
TNF - the cell proliferation gene
This gene encodes a multifunctional proinflammatory cytokine that belongs to the tumor necrosis factor (TNF) superfamily. This cytokine is mainly secreted by macrophages. It can bind to, and thus functions through its receptors TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR. This cytokine is involved in the regulation of a wide spectrum of biological processes including cell proliferation, differentiation, apoptosis, lipid metabolism, and coagulation. This cytokine has been implicated in a variety of diseases, including autoimmune diseases, insulin resistance, and cancer. Knockout studies in mice also suggested the neuroprotective function of this cytokine.
PPAR-γ2 – the regulatory gene
This gene encodes a member of the peroxisome proliferator-activated receptor (PPAR) subfamily of nuclear receptors. PPARs form heterodimers with retinoid X receptors (RXRs) and these heterodimers regulate transcription of various genes. Three subtypes of PPARs are known: PPAR-alpha, PPAR-delta, and PPAR-gamma. The protein encoded by this gene is PPAR-gamma and is a regulator of adipocyte differentiation. Additionally, PPAR-gamma has been implicated in the pathology of numerous diseases including obesity, diabetes, atherosclerosis and cancer.