CYP3A4 Gene: Impacting Prescription Drugs

Our bodies break down (metabolize) drugs and other toxins through a group of enzymes known as the CYP450 family. Different CYP enzymes break down different substances, and we all carry genetic variants that can impact whether we metabolize a drug quickly or slowly.

CYP3A4 and CYP3A5 enzymes and drug metabolism:

The CYP3A genes, which code for enzymes of the same name, are a subfamily of CYP 450. The CYP450 enzymes are used by the body to break down and eliminate many different toxicants and medications.

CYP3A4 or CYP3A5 metabolizes about half the drugs on the market today as well as other xenobiotics and steroids. When you take a medication, the length of time that a drug stays in your system is determine by how quickly your body breaks it down and excretes it.

There are genetic variants, or SNPs, in the CYP3A family that alter the function of the enzymes.

These variants impact how you react to a medication.

For example, if you don’t break down a medication as quickly, you may need less of the medication over time. Similarly, if you metabolize a medication more quickly than normal, you may need to alter the timing or change the dosage.

CYP3A4 and Grapefruit:

Several fruits – grapefruit, noni, pomegranate – are potent inhibitors of CYP3A4.

This means that the fruit blocks the enzyme from working. Eating or drinking grapefruit, noni, or pomegranate can cause adverse effects on drug metabolism, either increasing the efficiency of the drug or decreasing the effect.

Interestingly, the CYP3A4 enzyme is naturally more active in women than in men.

Commonly prescribed drugs metabolized by CYP3A4

Here are a few of the more commonly prescribed drugs that are metabolized using the CYP3A4 enzyme:

  • Viagra
  • Xanax
  • Cialis
  • Zocor
  • Prednisone

Methadone dosages can also be impacted by this gene.[ref]

A long list of drugs metabolized by CYP3A4 is available on Pharmacy Times and on  Wikipedia.


Genetic variants that impact CYP3A4 and CYP3A5:

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Please note that not all CYP variants are covered by 23andMe or AncestryDNA data. For a complete picture, talk with your doctor about pharmacogenetic testing.

CYP3A4 Gene Variants

Check your genetic data for rs4987161 (23andMe v4, v5):

  • G/G: CYP3A4*17, decreased function of enzyme[ref][ref]
  • A/G: carrier of one CYP3A4*17 allele
  • A/A: typical

Members: Your genotype for rs4987161 is .

Check your genetic data for rs4986909 (23andMe v4; AncestryDNA):

  • A/A: CYP3A4*13, decreased function of the enzyme[ref]
  • A/G: carrier of one CYP3A4*13 allele
  • G/G: typical

Members: Your genotype for rs4986909 is .

Check your genetic data for rs2740574 (23andMe v4,v5; AncestryDNA):

  • C/C: CYP3A4*1B, altered function of the enzyme[ref]
  • C/T: carrier of one CYP3A4*1B allele
  • T/T: typical

Members: Your genotype for rs2740574 is .

Check your genetic data for rs4986910 (23andMe v4, v5):

  • G/G: CYP3A4*3, decreased function
  • A/G: carrier of one CYP3A4*3 allele
  • A/A: typical

Members: Your genotype for rs4986910 is .

Check your genetic data for rs4986907 (23andMe v4, v5):

  • T/T: CYP3A4*15A, decreased function
  • C/T: carrier of one CYP3A4*15A allele
  • C/C: typical

Members: Your genotype for rs4986907 is .

 

CYP3A5 Gene Variants

CYP3A5 is another enzyme that is found in the liver, prostate, and intestines. The vast majority of Caucasians have a genetic variant (rs776746) that decreases the functionality of this enzyme.

Most of the drugs metabolized through CYP3A4 are also metabolized by CYP3A5. So if you are a poor or non-functioning CYP3A5 metabolizer but have functioning CYP3A4 genes, you may be just fine. 

Since the majority of several population groups have non-functioning variants for this gene, NOT carrying a variant may impact your metabolism of certain drugs by increasing enzyme function.[ref]

In addition to several types of drugs, CYP3A5 also metabolizes testosterone, progesterone, and androstenedione.[ref]

 

Check your genetic data for rs776746 (23andMe v4, v5; AncestryDNA):

  • C/C: CYP3A5*3, non-functional –most common type in Caucasians–
  • C/T: carrier of only one CYP3A5*3 allele (thus some CYP3A5 function)
  • T/T:  typical function

Members: Your genotype for rs776746 is .

Check your genetic data for rs28365083 (23andMe v4, v5; AncestryDNA):

  • T/T: CYP3A5*2, non-functional
  • G/T: carrier of one CYP3A5*2 allele (thus some CYP3A5 function)
  • G/G: typical  function

Members: Your genotype for rs28365083 is .

Check your genetic data for rs55817950 (23andMe v4, v5; AncestryDNA):

  • A/A:  CYP3A5*8, non-functional
  • A/G: carrier of one CYP3A4*8 allele (thus some CYP3A5 function)
  • G/G: typical function

Members: Your genotype for rs55817950 is .

Check your genetic data for rs28383479 (23andMe v4, v5):

  • T/T:  CYP3A5*9, non-functional
  • C/T: carrier of one CYP3A4*9 allele
  • C/C: typical

Members: Your genotype for rs28383479 is .

Check your genetic data for rs41279854 (23andMe v4, v5; AncestryDNA):

  • G/G:  CYP3A5*10, non-functional
  • A/G: carrier of one CYP3A4*10 allele (thus some CYP3A5 function)
  • A/A: typical function

Members: Your genotype for rs41279854 is .

Check your genetic data for rs56244447 (23andMe v4, v5; AncestryDNA):

  • C/C:  CYP3A5*3D, non-functional
  • A/C: carrier of one CYP3A4*3D allele (thus some CYP3A5 function)
  • A/A: typical function

Members: Your genotype for rs56244447 is .


Lifehacks:

If you carry one or two copies of a CYP3A4 variant that is non-functioning, this may impact the way medications work for you.  Look through the list of drugs metabolized by this enzyme and talk with your doctor or pharmacist.  (Keep in mind that 23andMe and AncestryDNA do not guarantee accuracy for medical purposes. Your doctor may want to run a second test to confirm.)

Grapefruit, noni, and pomegranate juices are inhibitors of CYP3A4 and CYP3A5. If you carry any of the genetic variants above for CYP3A4, be very careful of these juices or other inhibitors when taking a medication that is metabolized through CYP3A4.

St. John’s Wort is an inducer of CYP3A4, meaning it causes more of the enzyme to be created in the body. If you are taking a drug that is metabolized by CYP3A4, then you need to be careful with St. John’s wort interacting with the medication. (Talk with a doctor or pharmacists)[ref]

Members: Check your other detoxification genes on the Detox Topic Summary Report


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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.