Genetic Testing in Cardiovascular Diseases

There are a number of key genetic tests that can be used to determine risk factors. Just because you have a specific genotype, it does not mean you are going to get CVD, but does give you further information to reduce risk factors.

1. 9p21
2. Apo E
3. KIF6 
4. IL-1
5. Hg (Check if diabetic or suspect diabetes)

9P21 Genotype: Identifies Carriers of the Heart Attack Gene

• 9P21 gene, often called “The heart attack gene”
• An independent predictor of cardiovascular event risk even when such factors as family history, diabetes, high blood pressure, elevated levels of the inflammatory marker C-reactive protein, and obesity are taken into account.
• About 25 percent of Caucasians and Asians are homozygous for 9P21, meaning that they have inherited the gene from both their mother and father. 
• Studies link this genetic profile to a:
• 102 percent rise in risk for suffering a heart attack or developing heart disease at an early age, compared to non carriers of the gene.
• 56 percent overall increase in lifetime heart attack and heart disease risk.
• Much higher risk for severe coronary artery disease (CAD), affecting multiple arteries, both at a young age or over a lifetime.
• 74 percent jump in risk for aortic abdominal aneurysm, a weak, ballooning area in the heart’s largest blood vessel that’s often fatal if it ruptures.
• 400 percent increase in risk for CAD—and double the disease risk.
• Much higher risk for severe coronary artery disease (CAD), affecting multiple arteries, both at a young age or over a lifetime.
• 74 percent jump in risk for aortic abdominal aneurysm, a weak, ballooning area in the heart’s largest blood vessel that’s often fatal if it ruptures.
• 400 percent increase in risk for CAD (coronary artery disease)—and double the risk of death in the next 10 years—in people with poorly controlled diabetes, compared to diabetic non carriers with poor glycemic control.
• About 50 percent of Caucasians and Asians are heterozygous for 9P21. Since they only carry one copy of the gene (inherited from one parent), studies calculate that they have half the risk of each of the out-comes above. The frequency of this gene in African Americans and other populations has not yet been determined.

Apo E Genotype: Predicts Heart Disease and the Best Diet to Avoid It

• Apolipoprotein E (Apo E) genotype, which influences lifetime risk for coronary heart disease and Alzheimer’s disease, as well as how your body metabolises nutrients in your diet, including fats and carbs
• The Apo E gene has three variants (E2, E3, and E4), resulting in six possible genotypes: 
  1. 1. Apo E 2/2
     2. Apo E 2/3
     3. Apo E 2/4
     4. Apo E 3/3
     5. Apo E 3/4
     6. Apo E 4/4
• The Apo E 2/2 and 2/3 genotypes, which occur in 11 percent of the population, are associated with the lowest risk for CVD. If you have one of these genotypes, your best bet for disease prevention is a moderate-fat diet containing about 35 percent fat from heart-healthy sources, such as omega-3 rich oily fish or olive oil.
• People with the Apo E 2/4 and 3/3 genotypes, which are found in 64 percent of the population, have intermediate cardiovascular disease risk and benefit from the conventional “Mediterranean-style” diet that’s typically advised to protect heart health. This diet should contain about 25 percent fat.
• About 25 percent of people, have the Apo E 3/4 or 4/4 genotypes, which are linked to the highest lifetime risk for CVD. This group can trim the threat by following a very low-fat diet (no more than 20 percent fat) and limiting or avoiding alcohol consumption.
• The Apo E gene has an impact on exercise on the magnitude of the cholesterol surge that occurs after a meal. In a recent study in which people with various Apo E genotypes exercised then ate 500 calories of food 30 minutes later, those with the Apo E 2/3 genotype had the smallest rise in lipid levels. 
• People with the Apo E 3/3 genotype also benefited from exercising before the meal, but to a lesser extent, while people with Apo E 3/4 didn’t have any change in their cholesterol surge. (The study didn’t include people with 2/4 or 4/4 genotypes.)
• Controlling cholesterol is especially important for people with the Apo E 4/4 genotype. Research shows that middle-aged adults with total cholesterol levels of 240 mg/dL or higher were 60 per-cent more likely to develop AD decades later, while people with readings of 200 to 239 had a 52 percent jump in risk.

KIF6 Genotype: Predicts Statin Response and Heart Attack Risk

• The KIF6 gene’s job is to make a protein that transports other substances, such as protein complexes, within cells. Which version of the gene you carry influences both your risk for a heart attack
• There’s controversy about the effect of the KIF6 variant on lifetime CVD danger. In five large studies, un-treated carriers of the variant were at up to 55 percent higher risk for heart attacks, strokes, or death from cardiovascular causes, compared to un-treated participants without the variant.
• In two clinical trials, carrying the variant had a bigger impact on raising heart disease risk than being older than age 55, abnormal levels of LDL or HDL cholesterol, or high blood pressure. Only smoking and diabetes trumped the KIF6 mutation for boosting disease risk.

Interleukin 1 (IL-1) Genotype: Escalates the Body’s Inflammatory Response

• This genetic test checks for two genes, interleukin-1A (IL-1 A) and interleukin-1B (IL-1B) that regulate the interleukin-1 family of cytokines.
• These variants are linked to heightened response to inflammation, the immune system’s defense against injuries and infections. 
• Since these genes are among the first to be activated during the body’s inflammatory response, they ignite a chain reaction in which other inflammatory chemicals are released at higher-than-normal levels to escalate and sustain the blaze.
• As a result, carriers of these genes have a more-intense acute response to any type of inflammation and are also more prone to chronic inflammation.

Haptoglobin Genotype: Predicts Cardiovascular Danger in Diabetics

• Checks for variants of the haptoglobin (Hg) gene
• Provides valuable information if you have diabetes
• Raises the lifetime threat of CVD as much as smoking does
• Research suggests that you can almost entirely eliminate this increased risk by taking a (natural) vitamin E supplement.
• The Hg gene regulates haptoglobin, a protein produced by the liver that binds to hemoglobin, a sub-stance produced when red blood cells die.
• If hemoglobin isn’t bound quickly, it will release iron, which can harm arterial health in several ways.
  1. 1. The iron will oxidize LDL cholesterol, making LDL more harmful to your arteries. When Hg binds to hemoglobin, white blood cells can quickly clear this damaging substance from the bloodstream, neutralizing these threats.
     2. In diabetics, hemoglobin will also attach to HDL, negating many of its protective properties. 
• A particular genetic variant of Hg known as 2-2 does not bind well with hemoglobin, but what does get bound to it sticks to HDL extremely well! Therefore, Hg 2-2 packs a dual punch of bad news.
• Hp production is genetically controlled and varies by genotype. The Hg gene has two alleles, called Hg1 and Hg2. Since you inherit one allele from each parent.
• Three possible combinations.
  1. 1. Hg 1-1 (low risk)
     2. Hg 2-1 (intermediate risk)
     3. Hg 2-2 (high risk)
• If you have the 2-2 genotype, your lifetime risk for CVD is triple that of a diabetic with the 2-1 genotype, and five times higher than that of a diabetic with the 1-1 genotype. 
• About 16 percent of people carry the Hg 1-1 genotype, 48 percent carry Hg 2-1, and 36 percent carry Hg 2-2.
• Researchers have demonstrated, however, that type 2 diabetics with the Hg 2-2 genotype can counteract almost all the increased risk by taking 400 i.u. of the antioxidant vitamin E daily (natural form vitamin E such as found in Cod Liver
• Studies show that unless you’re a diabetic with this specific Hg gene variant, taking vitamin E may not have cardiovascular benefits and taking synthetic vitamin E may even increase risk factors.

 

References:

1. https://www.ncbi.nlm.nih.gov/pubmed/22015375
2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4129647/
3. Beat the Heart Attack Gene : The Revolutionary Plan to Prevent Heart Disease, Stroke, and Diabetes https://www.bookdepository.com/Beat-the-Heart-Attack-Gene/9781681620220/?a_aid=integratedperformanc