Genetic polymorphisms: how your DNA affects drugs

Ever take a drug that didn’t work or gave you unexpected side effects? Your genes can be the reason. Genetic polymorphisms are small DNA differences between people that change how the body handles medicines. Knowing the common ones can help you and your doctor choose safer, more effective treatments.

How polymorphisms change drug responses

Genes often control enzymes that break down medicines. When those genes vary, the enzyme can work too fast, too slow, or not at all. That changes the drug level in your blood and how well it works.

Here are clear examples you might run into:

• CYP2D6: Affects codeine and tramadol. Poor metabolizers may get little pain relief; ultra-rapid metabolizers risk strong effects or breathing problems.
• CYP2C19: Impacts clopidogrel (a blood thinner) and some antidepressants. Some people don’t convert clopidogrel to its active form, lowering protection after stents.
• TPMT: Tells how you handle azathioprine and mercaptopurine. Low TPMT activity raises the risk of bone marrow suppression unless doses are changed.
• HLA variants (for example HLA-B*57:01 or HLA-B*15:02): Linked to severe allergic reactions with drugs like abacavir or carbamazepine.
• VKORC1 and CYP2C9: Important for warfarin dosing—these variants guide initial dose and monitoring.

If a test shows a risky variant, your clinician can switch drugs, adjust dose, or increase monitoring. That one change can prevent harm or improve results.

How to get tested and what to ask

You can get pharmacogenetic testing through your doctor, a hospital lab, or some direct-to-consumer services. Clinical labs give reports that doctors can act on. If you try a DTC test, ask whether it checks the specific genes your medicines depend on and whether the lab is accredited.

Questions to bring up with your provider or pharmacist:

• Which genes matter for my current medicines?
• How will results change my prescription or dose?
• Where will my test results be stored and who can see them?

Don’t stop or change medications on your own. Use test results as a tool in conversation with a clinician. If you buy meds online, keep a record of genetic results and share them when a prescription is required—a pharmacist can flag drug choices based on your genetics.

Want practical reads? Check our articles on drug safety, dosing tips, and specific medications to see how genetics might matter for treatments you’re already taking.