“Take two aspirin and call me in the morning.”
That statement used to be a popular way to characterize the practice of medicine, back in the golden age of pharmaceuticals when drugs were seen as the answer to all problems. These days, we know that the picture is more complicated — some conditions remain stubbornly untreatable, and the treatments we do have don’t always work the same way for everyone. For some people, certain drugs might be more effective, or not work at all, or even produce serious side effects.
At least part of the reason is genetic, and with 23andMe’s Drug Response reports, you can learn about research that links your genetics to the way you might respond to certain drugs and medications. The results range from whether you’re likely to benefit from a drug, need a different dose due to sensitivity, experience toxic or adverse effects, or even have increased risk for other conditions.
23andMe’s 4-star Drug Response reports are structured very similarly to the Carrier Status reports discussed in the previous post, with information about the drug and how our bodies respond to it in the How It Works tab, and details about the genetic variants tested and how they influence drug response in the Technical Report tab, both located near the top of the page under the title of the report. Your results for that report’s drug response are found in a table in the section called “Your Genetic Data.”
My 4-star Drug Response reports are ranked in the dashboard according to whether my results for those reports are typical or not. Three reports — Warfarin (Coumadin®) Sensitivity; Clopidogrel (Plavix®) Efficacy; and Alcohol Consumption, Smoking, and Risk of Esophageal Cancer — show atypical results.
Warfarin (Coumadin®) Sensitivity
One of the most well-known genetically-influenced drug responses is that for warfarin (also called Coumadin®), a commonly prescribed blood thinner used to prevent the formation of blood clots. (Read more about the story of warfarin.) The appropriate dose for warfarin is notoriously difficult to determine, as two people who seem very physically similar may need very different amounts of the drug to achieve the same effect. Inaccurate dosing can also lead to serious consequences — too much, and the individual risks uncontrolled bleeding; too little, and dangerous blood clots may still form. Over the last decade or so, scientists have uncovered several genetic factors that influence a person’s sensitivity to warfarin, which can be used to determine an initial dose more accurately. My own results suggest that should I ever need to take warfarin, my physician may want to start me on a lower dose than usual.
Clopidogrel (Plavix®) Efficacy
Clopidogrel is another commonly prescribed blood thinner used to prevent blood clots that cause heart attacks and stroke. Some people, however, don’t receive the same benefit from the drug as other people. In order for the drug to work, it must first be absorbed into the intestine and then converted into its active form by liver enzymes. Certain genetic variations can inhibit or block one or more steps in this process, leading to insufficient quantities of the active form to produce the desired effect of the medication. My own results indicate that I have a genetic variant that could make clopidogrel less effective for me, so should I ever be at risk for a heart attack or stroke, my physician may want to prescribe an alternate therapy, such as aspirin.
Alcohol Consumption, Smoking, and Esophageal Cancer
This report links alcohol consumption and cigarette smoking to an increase in risk for esophageal cancer. Here, the drugs involved are not medical drugs, and the body’s ‘response’ is its risk for a health condition rather than efficacy, sensitivity, or toxicity. The genetic variant analyzed in the report is the same one associated with the “alcohol flush” trait commonly seen in East Asians (and also presented in 23andMe’s Alcohol Flush Reaction trait report). This variant disrupts a protein that normally helps break down toxic byproducts of alcohol, causing the byproduct to build up in the body; people with one copy of the variant have a reduced ability to break down the byproduct, while people with two copies cannot break it down at all. The same toxic byproduct is also found in cigarette smoke. It turns out that people with one or two copies of this genetic variant are at increased risk for esophageal cancer — and the risk is even higher if they are heavy drinkers or smokers. I’ve known for a long time that I flush when I drink alcohol (I have one copy of the disruptive gene variant), and now I’ll be even more mindful to drink only in moderation!
I have typical results for the other 4-star Drug Response reports:
Abacavir Hypersensitivity – Abacavir is a drug used to treat HIV/AIDS but a small percentage of people are hypersensitive to it. This reaction is linked to a specific genetic variant.
Fluorouracil Toxicity – 5-fluorouracil is a chemotherapy drug used to treat several types of cancer. It has very serious side effects in about 30% of people receiving it. Genetic variants in one specific gene are associated with increased risk for 5-fluorouracil toxicity.
Pseudocholinesterase Deficiency – Choline esters are a class of muscle relaxants commonly used in medical procedures, such as general anesthesia. Pseudocholinesterase is a protein that normally breaks down choline ester drugs. Certain variants in the gene for pseudocholinesterase disrupt its activity and cause an individual to experience the drug — and its effects — longer.
Response to Hepatitis C Treatment – The most common treatment for hepatitis C infection has a highly variable success rate. A genetic variant, however, influences your odds of responding favorably to this treatment.
Oral Contraceptives, Hormone Replacement Therapy and Risk of Venous Thromboembolism – Oral estrogen use in women — via oral contraceptives or hormone replacement therapy — has been associated with increased risk for venous thromboembolism (VTE), a potentially serious clotting disorder. Certain genetic variants also significantly increase your risk for VTE, so if you’re a woman taking oral estrogen, it’s important to know these risks as well as your status with regards to these variants. (Risk information for Venous Thromboembolism alone is also available as a Disease Risk report.)
Thiopurine Methyltransferase Deficiency - Thiopurine drugs are chemical compounds used to treat acute lymphoblastic leukemia, autoimmune diseases, and to prevent the rejection of transplanted organs. Thiopurine methyltransferase is a protein that helps convert thiopurines — which are quite toxic — into less harmful forms. Deficiency of this protein can cause an individual to experience serious side effects.
The information contained in the 4-star Drug Response reports has the potential to be very useful, but individuals should NOT start, stop, or change any treatment plans unless directed by a medical professional. It’s a good idea, however, to share your drug response reports with your physician so that he or she may make more informed decisions about your care.