Genelex Genetic Nutrition Analysis - The Science Explained

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Panel of Genes Tested

Apolipoprotein C-III gene (APOC3)
- Heart Health
APOC3 plays an important role in lipid metabolism. It inhibits the break down of triacylglycerol, a lipid, by the enzyme lipoprotein lipase; leading to higher triglyceride levels (hypertriglyceridemia). The polymorphism 3175G is associated with a four-fold risk of hypertriglyceridemia and is linked to an increased risk of heart attack, atherosclerosis and cardiovascular disease.

Cholesterol Ester Transfer Protein gene (CETP)
- Heart Health
The cholesterol ester transfer protein (CETP) is involved with HDL metabolism. It regulates the exchange of lipids between lipoproteins by transferring cholesterol from the HDL to other lipoproteins for uptake by the liver, leading to a reduced level of HDL. The polymorphism Intron 1 G279A increases the concentration of CETP and reduces the HDL levels. Reduced HDL levels are associated with an increased risk of cardiovascular disease.

Lipoprotein Lipase gene (LPL)
- Heart Health
Lipoprotein lipase is an enzyme that is involved in the metabolism of triglycerides in circulating lipoproteins. It enhances the uptake of lipoproteins and their content triglycerides by the liver and artery walls. The polymorphism C1595G appears to have a beneficial role as it has been linked with a decreased risk of cardiovascular disease, lower blood pressure and lower triglyceride levels.

Endothelial Nitric Oxide Synthase gene (eNOS)
- Heart Health
Endothelium-derived nitric oxide (NO) plays a key role in the regulation of vascular muscle tone; it also suppresses blood cell aggregation and adhesion. The polymorphism G894T may reduce nitric oxide bioavailability in the blood vessel wall and has been linked to the promotion of coronary atherosclerosis.

Methylenetetrahrdrofolate Reductase gene (MTHFR)
- Heart Health; Vitamin B Use
The MTHFR gene produces the key enzyme in folate metabolism. Folate (folic acid in it's synthetic form) is a water-soluble vitamin that is part of the B vitamin group. It is essential for DNA maintenance and repair, making new DNA when cells grow, and in the metabolism of amino acids (protein). Vitamin B6 and B12 are essential in folate metabolism; methionine, an amino acid, can be converted to and from homocysteine with the use of B12 and other molecules. Homocysteine is a harmful substance when it builds up in the blood, at higher levels it can lead to a condition called hyperhomocysteinemia, which can cause cardiovascular disease.

While performing its activity in cells, folate makes use of a molecular control mechanism: tiny 'tags', called methyl groups, without which cellular processes cannot proceed properly. These tags mark the sections of DNA that need to be repaired. Folic acid therefore prevents birth defects, making folate deficiency especially dangerous for pregnant women. There are a number of genes identified, which code for enzymes involved in the folate and homocysteine metabolic pathways.

This enzyme directs dietary folate to DNA synthesis or to convert homocysteine to methionine. There are two polymorphisms found commonly in the MTHFR gene, C677T and A1298C; both polymorphisms reduce the activity of this key enzyme. If the activity of the enzyme encoded by MTHFR is reduced, and there is not enough folate, B6 and B12 in your diet to supplement the reduction in activity, the wrong type of building blocks will get used to make new DNA. This DNA is weaker than it should be and your body becomes more vulnerable to disease. Moreover, without adequate support from the MTHFR enzyme, proper repair of existing DNA cannot take place and genes may be activated at the wrong times.

Reduced MTHFR activity can also lead to the build-up of a substance called homocysteine in the blood. High homocysteine levels have been linked to cardiovascular disease, venous thrombosis and neural tube defects in fetuses. These polymorphisms have also been associated with cervical, breast and esophageal cancers.

These two polymorphism have both positive and negative effects associated with them. For example, research suggests that having the C677T polymorphism may lead to an decreased risk for colon cancer and a increased risk for neural tube defects.

Methionine Synthase gene (MTR)
- Heart Health; Vitamin B Use
The MTR gene codes for an enzyme that is involved in the conversion of homocysteine to methionine. This polymorphism, A2756G, increases the enzyme's activity, which affects the amounts of circulating levels of folate and homocysteine. Lower homocysteine levels result, along with a reduced risk of cardiovascular disease. In addition, A2756G has been shown to decrease the chances of neural tube defects in fetuses and venous thrombosis.

Metyhionine Synthase Reductase (MS_MTRR)
- Heart Health; Vitamin B Use
Metyhionine synthase reductase is an enzyme, which is necessary for the reformation of a derivative of vitamin B12. It is needed to maintain adequate cellular amounts of B12, methionine and folate, and to keep homocysteine levels down. This polymorphism, A66G, is associated with increased risk of cardiovascular disease, which is independent of homocysteine levels. There also appears to be an increased risk of neural tube defects, Spina bifida and Down syndrome in fetuses.

Cystathionine Beta Synthase (CBS)
- Heart Health; Vitamin B Use
CBS is an enzyme that is necessary to convert homocysteine to cystathione; it lowers homocysteine levels. Two polymorphisms, C699T and T1080C have been shown to increase the activity of the enzyme, and thus reduce the amount of homocysteine in the blood. These polymorphisms are associated with a decreased risk of coronary artery disease.

Glutathione S-Transferase mu, M1 (GSTM1)
- Detoxification; Antioxidant
This polymorphism results in a loss of function of the enzyme due to the loss of most of the coding region of the gene. It is suggested that this polymorphism might be associated with several health conditions: cancer, schizophrenia, bronchial asthma, and multiple sclerosis. It has been estimated that 17% of all lung and bladder cancers may be attributed to GSTM1 polymorphisms.

Glutathione S-Transferase theta, T1 (GSTT1)
- Detoxification; Antioxidant
This polymorphism results in a loss of function of the enzyme due to the loss of most of the coding region of the gene. The enzyme for this gene is found in a variety of tissues, including red blood cells, liver, kidney, and the lung. This polymorphism is associated with an increased risk of cancer, in particular lung, larynx, and bladder. The polymorphism has been linked with prostate cancer and an increased risk of cervical cancer.

Studies suggest that individuals with both GSTM1 and GSTT1 polymorphisms have a greatly increased risk of developing cancer. The combination of these two polymorphisms is also associated with an increased risk of primary dysmenorrhoea, and increased severity of bronchial asthma in children. Additionally having all three polymorphism may lead to an increased risk for breast cancer.

Glutathione S-Transferase P1, pi (GSTP1)
- Detoxification; Antioxidant
The GSTP1 gene is known to metabolize many carcinogenic compounds. Two polymorphism in the GSTP1 gene are A313G and C341T. The enzymes of these polymorphisms have a decreased level of activity. The A313G polymorphism has been associated with an increased risk for developing prostate cancer. It was also found at an increased level in women with recurrent early pregnancy loss. Polymorphisms in this gene have been suggested to be associated with asthma and muscular dystrophy.

Manganese Superoxide Dismutase (MnSOD)
- Heart Health; Antioxidant
The enzyme MnSOD is a free radical scavenger with antioxidant activity within the cell, particularly in the mitochondria. Two polymorphisms (variations from the normal gene) of this gene are: C(-28)T and T175C.

• C(-28)T
  This polymorphism affects the intracellular distribution of the enzyme by preventing the enzyme from entering the mitochondria within the cell. The polymorphism has been associated with increased risk for developing several diseases, in particular cancer and macular degeneration. Unexpectedly it is the absence of the polymorphism and not the presence of it; that is associated with an increased risk of developing disease. The unexpected benefit of having the polymorphism is attributed to the fact that the enzyme remains functional, but remains distributed within the cell rather than becoming concentrated in the mitochondria. The risk for developing a disease appears to decrease as the consumption of antioxidant rich nutritional sources increases.
  
  
• T175C
  This polymorphism reduces the stability of the active enzyme complex. The reduced activity may be as much as 3 times less than normal.

Superoxide Dismutase (SOD3)
- Heart Health; Antioxidant Activity
SOD3 is the major antioxidant enzyme of the blood vessel wall. The highest levels of SOD3 are found in the adult heart, placenta, pancreas and lung, followed by moderate levels in the kidney, skeletal muscle and liver. The polymorphism, C760G, has been shown to lead to the release of the enzyme SOD3 from the vessel wall into blood plasma and is accompanied by a reduction in tissue antioxidant activities. As such it has broad implications for coronary artery disease and may contribute to its development.

Research shows that SOD3 activities are decreased in subjects with low serum zinc concentrations. It is suggested that SOD3 activity may be a functional indicator of severe zinc nutritional deficiency.

Vitamin D receptor gene (VDR)
- Bone Health
Vitamin D plays an important role in maintaining calcium levels. It regulates bone cell growth and differentiation, intestinal calcium absorption and parathyroid hormone secretion.
Three polymorphisms (variations from the normal gene) of this gene are: Taq1, Bsm1, and Fok1.

• Taq1
  This polymorphism has been shown to increase bone turnover (replacing new old fatigued bone cells with new cells) resulting in a greater risk of low bone mineral density and for osteoporosis. In addition, it is also associated with the degeneration of non-mineralized connective tissue, which suggests that Taq1 has a greater impact than on just bone health.
  
  
• Bsm1
  This polymorphism has been linked to reduced bone mineral density and an increased risk for osteoporosis. It has been shown that for individuals with this polymorphism, dietary calcium supplementation is required to achieve the same bone density as individuals without the polymorphism. In addition, individuals with this polymorphism tend to be shorter in height. The absence of the Bsm1 polymorphism may have beneficial effects on bone health.Research studies have revealed conflicting results regarding Bsm1. The absence of this polymorphism is associated with beneficial effects on bone mass, however in contrast; the absence of the polymorphism is also associated with an increased risk of breast and prostate cancer, atherosclerotic coronary artery disease and primary hyperparathyroidism.
  
  
• Fok1
  Unlike Taq1, the absence of this polymorphism has been shown to increase bone turnover resulting in a greater risk of low bone mineral density and for osteoporosis. Some studies have been done indicating that the absence of Fok1 may predispose women to osteoporosis at the lumbar spine. This increased risk, maybe as much as 2.8 times normal.
  The vitamin D receptor gene has also been linked to cancer, osteoarthritis, hyperparathyroidism, diabetes, coronary artery disease, kidney stones, and infectious diseases like tuberculosis and hepatitis B.

Collagen type 1 alpha gene (COL1A1)
- Bone Health
This gene plays an important role in the production of the major protein of bone: Type 1 collagen. A polymorphism, Sp1, in this gene can result in decreased bone mineral density and decreased bone strength resulting in an increased risk of fractures. Dietary calcium can reduce the risks associated with having the polymorphism.

Interleukin 6 gene (IL-6)
- Bone Health; Heart Health; Inflammation
Interleukins are messenger molecules that are released by white blood cells when the body has an infection, disease or inflamed tissues. In response to LDL levels and arteriole damage, IL-6 is produced. IL-6 stimulates the liver to make reactive proteins, which are released into the blood. The polymorphism G174C appears to over stimulate protein production. High levels of this particular protein have been linked to an increased risk of elevated blood pressure and heart disease.

Interleukin-6 has some effect on stimulation of osteoclast resorption. Osteoclasts are the cells that actively reabsorb old or fatigued bone cells.
Two polymorphisms of this gene are: G-634C and G-174C.

• G-634C
  This polymorphism is associated with the lowest bone mineral density between the two Interleukin polymorphisms. It has been suggested that this polymorphism can lead to osteoporosis.
  
  
• G-174C
  This polymorphism is associated with lower bone resorption and may be a significant determinant of the risk for osteoporosis in elderly subjects.

Tumor Necrosis Factor alpha gene (TNFa)
- Bone Health; Inflammation
Like the IL-6 gene, the tumor necrosis factor alpha gene also has a stimulatory effect on osteoclast resorption. A polymorphism, G-308A, has been shown to have an effect on mineral metabolism in bone and can lead to an increased risk for osteoporosis.

This polymorphism (variation from the normal gene) increases the levels of inflammation and appears to be involved in many inflammation-related diseases and disorders. Some of these diseases and disorders are: arthritis, allergies, asthma, aging, chronic obstructive pulmonary disease, crohn's disease, obesity, osteoporosis and sepsis.

Angiotensin converting enzyme (ACE)
-Heart Health; Insulin Sensitivity
ACE plays an important role in blood pressure regulation and electrolyte balance. The ACE polymorphism has been associated with a large number of diseases including cardiovascular disease, cancer, diabetes and insulin resistance.

Peroxisome proliferators - activated receptor gamma gene (PPAR2)
-Insulin Sensitivity

The PPAR2 gene is a nuclear hormone receptor transcription factor and regulates the expression of several genes. It has a major role in adipogenesis (formation of fat) and expression of adipocyte (fat containing cells) specific genes. Studies support a beneficial role for the polymorphism, Pro12Ala. Pro12Ala may be associated with reduced transcription of the PPARgamma2 gene. It may also be associated with lower body mass index (BMI), lower fasting insulin levels, higher HDL levels and improved insulin sensitivity. Hence the Pro12Ala may decrease the risk for insulin resistance, type 2 diabetes and heart disease.

Insulin is a hormone that is crucial for normal functioning as it regulates glucose uptake by tissue, which is needed to supply energy. Insulin resistance leads to a diminished ability of the body to respond to insulin, thereby negatively affecting glucose utilization. To compensate for insulin resistance, the pancreas will produce more insulin hormone.

Insulin resistance syndrome is used to describe a combination of medical illnesses affecting the way the body uses insulin to metabolize sugars. There are several illnesses that can result from insulin resistance, these include: type 2 diabetes, obesity, high blood pressure, abnormal cholesterol levels, and heart disease. It is estimated that these insulin resistance disorders affect approximately 70 to 80 million Americans.

It is estimated that for people with high blood pressure that is not directly caused by a disease, 50% of these people may have insulin resistance syndrome. Research suggests that the higher the blood pressure is, the greater the insulin resistance is.

In general, insulin resistance and impaired insulin secretion cause type 2 diabetes. As long as the pancreas can produce enough insulin to compensate for the degree of insulin resistance, glucose tolerance remains normal. Clustering of type 2 diabetes in certain families and ethnic populations, point to a genetic linkage. Usually environmental factors like obesity and a sedentary lifestyle are required to unmask the genes.