The Science Of Testing
When you gently brush the inside of your cheek with the GnomeDX cotton swab, you gather some of your cheek cells. Inside of each cell are your chromosomes, one from each of your parents. Chromosomes are made up of DNA. Segments of DNA are called genes. Genes act as instructions for proteins and are required for your cells, tissues and organs to function.
Not everyone’s genes are exactly the same. The building blocks of those genes (called nucleotides) can be switched, added, or deleted. These variations make up your unique sequence which can affect how you respond to medicine. Your unique sequence is what we determine in your GnomeDX results.
Based on your sequence, your proteins can function differently, therefore processing (metabolizing) medications differently. For example some people are normal metabolizers, meaning the drugs they take work like they are supposed to. However, many people are either intermediate, poor or rapid metabolizers which can increase risk of negative side effects or show no improvement for your health, depending on the type of drug.
It's important for your doctor to know what type of metabolizer you are for a specific set of drugs so they can avoid medications that could harm you, or not work at all.
The CardiacDX test covers 12 genes
About this test
There are two genes primarily involved in warfarin PGx. The first is VKORC1, the protein that warfarin acts upon to achieve therapeutic effect. The second is CYP2C9, the liver enzyme that metabolizes warfarin so it can be cleared from the body (11). A 2010 study of 10,000 patients found that 69% had at least one actionable variant related to warfarin dosing (11). CPIC and the FDA issue the same recommendations for genotype-guided warfarin therapy, covering every combination of CYP2C9 and VKORC1 status (11). Good metabolizers with normal sensitivity receive the standard dose: 5-7 mg. For poor metabolizers with increased sensitivity that dosage would be a 10-fold overdose, putting them at risk for a bleed - the most clinically significant complication with warfarin therapy.
Clopidrogrel is a prodrug which must be activated in the liver to achieve therapeutic effect. However, 25% of Caucasians, 30% of Blacks, and 50% of Asians (12) have a variant which decreases the function of CYP2C19, the liver enzyme responsible for that activation. These patients have significantly higher rates of cardiovascular death, myocardial infarction or stoke, and very significantly higher rates of stent thrombosis because less of the drug gets activated in their systems (7). Studies show by adjusting treatment, clinicians can spare their patients from these increased risks (13). CPIC has published guidelines recommending alternative therapy for poor and intermediate CYP2C19 metabolizers. The same recommendation has been issued by the FDA as a black box warning on the clopidogrel label.
A quarter (25.7%) of the US population has a variant decreasing the expression of the SLCO1B1 protein (11). This protein is responsible for transporting simvastatin into the liver to achieve therapeutic effect and to be cleared from the body. Without access to the liver, the drug stays in the blood longer, affecting the skeletal muscle and causing the most common adverse effect, myopathy (14, 8). Myopathy is also the leading cause of poor patient adherence to their drug regimen.
The magnitude of the effect is comparable to drinking grapefruit juice. Both drinking grapefruit juice (15, 10) and having the SLCO1B1 variant gene (16) cause 3x increase in drug exposure. Just as there are guidelines to adjust dosage/drug because of grapefruit juice, there are also published CPIC guidelines that recommend decreased dosage or choosing a different statin (less reliant on the SLCO1B1 transporter) for patients with the SLCO1B1 variant (17).