Say you aren’t feeling well, have had a cold for a week, and can’t sleep… You’re just plain miserable. And in your sleep-deprived state, you decide to take some Nyquil (or another cough syrup containing dextromethorphan).
Some people may get relief and finally get some sleep. Others… well, they may not react the same way to dextromethorphan! I know several people who have bad reactions to cough medicine, waking up the next morning feeling like they were hit by a truck.
This is just one example, among many, of medications that are metabolized by the CYP2D6 enzyme. There are many genetic variants that impact the function of CYP2D6 which causes a wide variety of reactions to some commonly used medications.
The CYP2D6 enzyme metabolizes (breaks down) about 25% of pharmaceutical drugs including SSRIs, opioids, tamoxifen, dextromethorphan, and beta-blockers.
Here is a partial list of drugs metabolized by CYP2D6:
There are several important variants in the CYP2D6 gene which can cause the enzyme to function differently — either speeding up or slowing down the rate at which medications are broken down.
A variant that slows down the CYP2D6 isn’t always bad. Being a poor metabolizer may reduce the risk of some cancers such as bladder or lung. On the other hand, it also may significantly increase the risk of Parkinson’s disease for those exposed to pesticides.
Knowing whether you’re a fast or slow metabolizer may make it easier to find the right dosage of certain medications. But you also need to know how the drug works in the body:
Keep in mind that many drugs, toxins, and endogenous substances can be metabolized using multiple different CYP enzymes. Thus, many drugs metabolized by CYP2D6 may also be broken down with other enzymes.
Members: Your genotype for rs3892097 is —.
Members: Your genotype for rs5030655 is —.
Members: Your genotype for rs5030656 is —.
Members: Your genotype for rs1065852 is —.
Members: Your genotype for rs28371725 is —.
Members: Your genotype for rs1135824 is —.
Members: Your genotype for rs5030867 is —.
Members: Your genotype for rs28371706 is —.
Members: Your genotype for rs16947 is —.
There are other (rare) variants for CYP2D6 not covered by 23andMe or AncestryDNA. Thus, the above list does not cover all gene variants.
The main take-away here is that if you carry a non-functioning variant, you need to be aware that drugs metabolized through CYP2D6 may not work as well for you.
There are also substances that inhibit the CYP2D6 enzyme.
CYP2D6 Inhibitor + CYP2D6 genetic variant = problems (maybe)
Common CYP2D6 inhibitors include:
Talk with your doctor or pharmacist if you have questions. I don’t want to steer anyone wrong here, but I do think it is important for people to know that their genetic variants impact drug metabolism rates.
Originally published 6/2015. Revised on 4/26/19.