CYP2B6: Genetic variants impacting medication reactions

The CYP2B6 enzyme is part of the body’s first line of defense in detoxifying and breaking down certain substances. It is one in the family of CYP450 enzymes, and CYP2B6 is important for metabolizing several medications.

CYP2B6, genetics, and medication interactions:

Genetic variants in the CYP2B6 gene cause large variations in how the enzyme works. For some people, genetic variants cause significant decreases in enzyme function, while others may have faster enzyme function.[ref]

Drugs metabolized by CYP2B6 include:[ref][ref]

  • methadone
  • bupropion
  • ketamine
  • cyclophosphamide
  • artemisinin
  • efavirenz – HIV medication
  • nicotine (along with CYP2A6)[ref]
  • sertraline – Zoloft (along with other CYP enzymes)[ref]
  • estrone and 17beta-estradiol (along with other CYP enzymes)[ref]

In general, CYP2B6 enzyme function is a little higher in women than men.[ref]

What does CYP2B6 do besides breaking down medications?

An animal study in mice shows that reduced CYP2B6 function causes problems with metabolizing corn oil. The mice with reduced CYP2B6 function ended up becoming more obese and having higher triglycerides and cholesterol (compared to normal mice) when fed a bunch of corn oil.[ref] Keep in mind that this is an animal study… I’m unable to find any research on humans with lower CYP2B6 and dietary interactions.


CYP2B6 Genetic Variants:

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The CYP2B6 enzyme metabolizes organophosphates at lower concentrations, such as from normal exposure to pesticide residue.[ref]

Check your genetic variants for rs3745274 G516T (23andMe v.4; AncestryDNA):

  • T/T: CYP2B6*6, decreased activity[ref][ref] may need a lower dose of efavirenz (HIV medication)[ref][ref] slower clearance of ketamine[ref]
  • G/T: somewhat decreased activity
  • G/G: typical

Members: Your genotype for rs3745274 is .

Check your genetic data for rs2279343 K262R (23andMe v5):

  • G/G CYP2B6*6, decreased activity[ref][ref] may need a lower dose of efavirenz (HIV medication)[ref][ref]; slower clearance of ketamine[ref]
  • A/G: somewhat decreased activity
  • A/A: typical; better response to quitting smoking[ref]

Members: Your genotype for rs2279343 is .

Check your genetic data for rs28399499 C983T (23andMe v4, v5; AncestryDNA):

  • C/C: significantly reduced enzyme activity; 3x increased risk of adverse drug reactions with efavirenz (may need a lower dose)[ref][ref]
  • C/T: reduced enzyme activity
  • T/T: typical

Members: Your genotype for rs28399499 is .

Check your genetic data for rs3211371 T1459C (23andMe v4):

  • T/T: reduced function, especially in women[ref]
  • C/T: reduced function, especially in women
  • C/C: typical

Members: Your genotype for rs3211371 is .

 


Lifehacks:

If you are taking a medication that is metabolized using CYP2B6, talk with your doctor or pharmacist if you have questions about the dosage.

If you are a slower CYP2B6 metabolizer, interactions with other medications may become more important. For example, clopidogrel (Plavix) also inhibits the CYP2B6 enzyme.[ref]

Curcumin, a popular anti-inflammatory supplement, is an inhibitor of CYPB6.[ref] If you have variants that slow down CYP2B6, taking a curcumin supplement along with a medication metabolized by CYP2B6 may impact the way the medication works.

Astragalus is another natural supplement that inhibits CYP2B6.[ref]


Related Articles and Topics:

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Learn how the different genetic variants in phase I and phase II detoxification genes impact the way that you react to medications and break down different toxins.

CYP2C9: Breaking down prescription medications
Have you ever wondered why certain medications don’t work well for you? Genetic variants can change how fast or how slow the medication is broken down in your body. Learn how the CYP2C9 variants impact quite a few prescription medications.

Nrf2 Pathway: Increasing the body’s ability to get rid of toxins
The Nrf2 (Nuclear factor erythroid 2–related factor) signaling pathway regulates the expression of antioxidants and phase II detoxification enzymes. This is a fundamental pathway that is important in how well your body functions. Your genetic variants impact how well this pathway functions.




Author Information:   Debbie Moon
Debbie Moon is the founder of Genetic Lifehacks. She holds a Master of Science in Biological Sciences from Clemson University and an undergraduate degree in engineering from Colorado School of Mines. Debbie is a science communicator who is passionate about explaining evidence-based health information. Her goal with Genetic Lifehacks is to bridge the gap between the research hidden in scientific journals and everyone's ability to use that information. To contact Debbie, visit the contact page.