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I have stars in my genome! Or how genetic variations affect your drug response

How drugs affect the body

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Many commonly used drugs can be helpful for most while causing adverse reactions in others. Medication needs to be absorbed and then metabolized into a biologically active form or inactivated at a certain rate. Drug absorption and secretion (i.e. pharmacokinetics) can be affected by certain genetic variations that may render medication ineffective or dangerous for you.

This post aims to:

  • Help you to find the right medications for you
  • Explain how drugs react with the body

How to find which medications are right for you?

Knowledge of drug-gene interactions (pharmacogenetics) can help you to avoid taking the wrong drug or wrong dose.

How pharmacogenetics works?

Imagine your body is a pool with pipes bringing water in and out. Water levels in the pool reflect the amount of a specific medication in your blood. Water being taken in represents you swallowing pills at a prescribed rate (once or twice daily), the pills dissolving in your stomach, and then going into your blood stream. Water being drained signifies your liver metabolizing the drugs and the kidneys removing them from your body.

If the intake pipe is blocked or too narrow as a result of reduced drug absorption in your gut, not enough of the drug is metabolized to be effective – you cannot swim in ankle deep water. When your liver is affected by alcohol, fatty diet, age, or other medications, the pool will overflow leading to major damage.

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Some people are born with less active cytochrome P450 (CYPs) liver enzymes that are essential for activation and detoxification of bioactive toxins. The mutations in specific CYP genes can make you more susceptible to specific medications. For example, people who have reduced activity or are in complete deficiency of the CYP2C19 gene cannot activate clopidogrel (aka Plavix) into an active form, are at higher risk of stroke and heart attacks. At the same time, people with reduced CYP2C19 activity (poor metabolizers) respond better to Proton Pump Inhibitors (PPIs).

Conversely, individuals with higher CYP2C19 levels (ultrafast metabolizers) benefit well from clopidogrel, but need a double or quadruple dose of PPI for treating ulcers.

Steps to find the right medications:

Step 1: Get a genetic test to determine your metabolic status

It’s important to be aware of the type of metabolizer you are for each cytochrome P450. This can give you essential information to help your health, like how much coffee you can drink before bed without getting a heart attack.

Step 2: Review your results

Typically, the results will come with annotations of specific mutations (alleles) that are genetic variations inherited from your mother and father. Each allele can be named as *1 or *2 or another “star number”. Sometimes the numbers are followed by letters for example *2B. The end result will be a combination of stars *1/*2B.

Step 3: Understand what the stars mean

After receiving your results, do not panic! The combinations of stars are historical annotations for calling different genetic variations. Most common variant *1 is considered “normal”, and *2 is a new type of genetic variation found to be genetically and/or functionally different from *1. If you have a *41 allele in CYP2D6, it means that it is one of rare mutations in this gene. If your stars (alleles) are different from the norm, a list of unique stars can be found via an international database that catalogues all variations in CYP genes. In most cases, the enzymatic activity of each allele is known through pharmacokinetic studies with medications metabolized with specific cytochrome.

Deriving meaning from your metabolic status

Your metabolic status is determined by the combination of both alleles. For example, if you inherited one normal copy (CYP2C19*1) from one parent and an inactive copy (CYP2C19*3) from another parent you will be considered an intermediate metabolizer for the CYP2C19*1/*3 gene, which tells your doctor that you are not a good candidate for clipodogrel.

How to get a genetic test?

You can test your DNA now to check how you will respond to over 60 medications to reduce the risk of adverse side effect to your current and future medications.

WHAT’S NEXT?

If you would like to learn more about the way your body responds to drugs, continue reading this related blog post: “How To Choose a Genetic Testing Provider”.

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Author: Ruslan Dorfman