Phase I Detoxification -CYP450 Genetics Report

The CYP450 family of enzymes break down hormones, medications, and toxins in what is known as Phase I of detoxification. These metabolites then go through a second phase of detoxification before being excreted by your body.

The genes listed below are some of the CYP450 enzymes that break down common medications. Variations in these genes cause the enzymes to function differently than normal: drugs can break down either more quickly than normal (rapid metabolizer) or more slowly than normal (poor metabolizer).

  • Highlights in yellow indicate that you have one of the variants (heterozygous).
  • Highlights in   red indicate that you have two of the variants (homozygous).

If your result is highlighted, click the “more info…” for the gene and read through the studies as well as clicking on the link for the substances (substrates) broken down by the gene.

This report is optimized for the 23andMe v.4 chip, so if you have 23andMe results from August 2017 forward, there may be blank results in places indicating that the information is not available on the newer v.5 chip.

Talk with your doctor if you have questions about medications.  Also, a lot of medications are metabolized through more than one pathway in the body so being a poor metabolizer for one CYP enzyme may not affect a drug that is metabolized through multiple enzymes.

These reports are offered on a ‘pay what you can’ basis:



rs ID Minor allele* Your results
CYP1A1 (more info…)
rs1048943 C
rs1799814 T
rs2606345 A
CYP1A2 (more info…)
rs762551 C
rs12720461 T
rs56276455 A
CYP1B1 (more info…)
rs1056836 C
rs1800440 C
CYP2A6 (more info…)
rs1801272 T
rs5031017 A
CYP2B6 (more info…)
rs3745274 T
CYP2C9 (more info…)
rs1799853 T
rs1057910 C
rs28371686 G
rs9332131 D
rs7900194 A
rs28371685 T
CYP2C19 (more info…)
rs12248560 T
rs4244285 A
rs4986893 A
rs28399504 G
rs56337013 T
rs72558186 A
rs41291556 C
rs6413438 T
CYP2D6 (more info…)
rs3892097 T
rs5030655 D
rs1135824 C
rs5030867 G
rs5030865 T
rs28371706 A
rs28371725 T
CYP2E1 (more info…)
rs2031920 T
CYP3A4 (more info…)
rs2740574 C
rs67784355 A
rs4987161 G
CYP3A5 (more info…)
rs28365083 T
rs776746 C
rs41303343 D
rs55817950 A
rs28383479 T
rs72552791 C

*Given in plus orientation

A good general list of drugs metabolized through CYP enzymes can be found on the Indiana University Dept. of Medicine site.

CYP1A1

CYP1A1metabolizes some drugs and xenobiotics in the liver.  It is also involved in the activation of aromatic hydrocarbons (PAH) in the intestines and thus may play a role in smoking-related cancers.   Aromatic hydrocarbons are also found in wood smoke, vehicle exhausts, asphalt, and charred meats.  Additionally, CYP1A1 also plays a role in metabolizing polyunsaturated fatty acids into signaling molecules, as well as a role in estrogen metabolism.  [Wikipedia]  [WikiGenes]

Dietary Interactions:  
Quercetin, a plant polyphenol, increases CYP1A1. [ref]

rs1048943, C is the minor allele, also known as CYP1A1*2C, A4889G

  • “results in a two-fold higher catalytic activity” [ref]
  • In non-smokers, those with the C/C genotype have 71% decreased risk of heart disease. [ref]
  • A A Chinese study showed that the CYP1A1*2 variant lowers the risk of breast cancer.
  • A German study showed that CYP1A1*2 has a higher activity level in estrogen metabolism.
  • A 2017 study shows that those with the C allele are at a lower risk of breast cancer, regardless of grilled or smoked meat (PAH) intake.[ref]

rs2606345, also known as CYP1A1  (G is minor allele)

  • subjects with the minor allele had a smaller chance of getting community-aquired pneumonia [ref]

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CYP1A2

CYP1A2 is involved in the metabolism of xenobiotics (caffeine, aflatoxin B1, and acetaminophen) and is induced by polycyclic aromatic hydrocarbons (found in cigarette smoke).  It metabolizes some PAH’s into carcinogenic intermediates.

Drug interactions:
There is a list of drugs, inducers, and inhibitors for CYP1A2 on Wikipedia.  Another good list and explanation can be found here.  For example, the common antibiotic, ciproflaxin, is a potent inhibitor of CYP1A2.

Dietary interactions:
CYP1A2 is induced by cruciferous veggies (such as cabbage, cauliflower, and broccoli) and coffee. It is inhibited by cumin, turmeric, peppermint, chamomile, dandelion, and St. John’s wort.

rs762551, also known as CYP1A2*1F

  • Several studies have concluded that the AA genotype is tied to faster metabolism of caffeine.  [ref]
  • A study on breast cancer found that “In conclusion, the CYP1A2*1F genotype significantly modified the relationship between coffee consumption and breast volume in non-users of hormonal contraception. It is likely that various compounds in coffee exert a direct effect on the breast epithelium. As breast volume is associated with breast cancer risk in lean women, our finding is compatible with earlier reports of a protective effect of coffee on breast cancer risk restricted to women with the CYP1A2*1F C-allele.” [ref]
  • more studies

rs12720461, also known as CYP1A2*1K, -730T

  • “Subjects with CYP1A2*1K had significantly decreased CYP1A2 activity in vivo…” [ref]

rs56276455, also known as CYP1A2*3,  2385G>A

  • Decreased enzyme expression [ref]

CYP1B1

CYP1B1 is involved in breaking down some drugs, cholesterol and other lipids, PAH, and 17beta-estradiol.  It is also involved in eye development and some mutations are associated with early onset glaucoma.

rs1056836, also known as V432L

  • A study of radiation technicians found that “the minor allele of CYP1B1 V432L significantly increased the dose-response relationship between personal diagnostic x-ray exposure and breast cancer risk, adjusted for cumulative occupational radiation dose”. [ref] (note that the orientation is flipped for 23andMe)
  • A small study of non-smokers found that “Among Caucasians, however, CYP1B1 Leu432Val was significantly associated with lung cancer susceptibility odds ratio (OR) for at least one valine allele = 2.87″ [ref]
  • more studies

rs1800440, also known as

  • A study of women using hormone therapy found that C allele carriers who had never used hormone therapy were at a decreased risk of breast cancer (OR=0.4) vs. women who had used hormone therapy (OR=1.2). [ref]
  • more studies

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CYP2A6

CYP2A6 is involved in the metabolism of nicotine, several cancer drugs,  and a few other drugs. (). The hormone estradiol is an inducer of CYP2A6, and women usually have somewhat higher activity of this enzyme.  It is thought that polymorphisms of CYP2A6 which cause decreased activity results in a lower level of dependence in smokers and makes it easier for them to quit.  Whereas those with increased enzyme activity have enhanced metabolism of nicotine and are more likely to smoke more cigarettes per day.  [ref]

Drug Interactions:
There is a list of drugs metabolized by CYP2A6 on Wikipedia.

Dietary Interaction:
Cinnamon inhibits CYP2A6. [ref]

rs1801272, also known as CYP2A6*2, 1799T>A

  • Carriers of the minor allele are less likely to be smokers (or addicted to nicotine). [ref] and [ref]
  • Slower metabolizer according to SNPedia.  40-50% activity for one copy, less than 40% activity for homozygous. [ref]

rs5031017, also known as CYP2A6*5

  • Homozygous (AA) is a non-functioning variant, according to SNPedia. [ref]
  • Poor metabolizer of nicotine. [ref]

CYP2B6

The CYP2B6 gene encodes the enzyme that metabolizes nicotine (along with CYP2A6) as well as other drugs.  It also is involved in the synthesis of cholesterol, breakdown of lipids, and some steroids.

Drug interactions:
List of drugs that interact with CYP2B6.

rs3745274, also known as CYP2B6*6,  516G>T

  • TT homozygous individuals had higher concentrations of Efavirenz (HIV drug that is metabolized through CYP2B6) [ref]
  • reduced expression of the enzyme (in reference to chlorpyrifos, pesticide)  [ref]

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CYP2C9

CYP2C9 metabolizes quite a few popular drugs (NSAIDs, warfarin, Viagra, Prozac) in the liver as well as linoleic acid, arachidonic acid, and serotonin outside of the liver.

Drug Interactions:
There are several polymorphisms in the CYP2C9 gene that change the activity level of the enzyme.  This is important when looking at how your body is going to respond to different doses of common drugs.  For example, with some loss-of-function variants of CYP2C9, people may have an increased risk of stomach bleeding with NSAIDs. [ref] A list of drugs metabolized by CYP2C9 can be found on Wikipedia.

Warfarin is a very popular anti-coagulant.  Dosage variations that are determined by genetic factors are mainly based on the CYP2C9 and VKORC1 genes.  There is a neat tool put out by Stanford that estimates Warfarin dose based on genetic polymorphisms.

rs1799853, also known as CYP2C9*2

  • Reduced function; heterozygous has 20% reduction in Warfarin metabolism, homozygous has 40% reduction in Warfarin metabolism. [ref]
  • Increased risk of acute gastrointestinal bleeding if using NSAId that is a CYP2C9 substrate.[ref]

rs1057910, also known as CYP2C9*3

  • Significantly reduced function; heterozygous has 40% reduction in Warfarin metabolism, homozygous has 80% reduction in Warfarin metabolism. [ref]
  • One study found: “A more than two-fold reduced oral clearance in homozygous carriers of CYP2C9*3 was seen for celecoxib compared to carriers of the wild-type” [ref]

rs28371686, also known as CYP2C9*5

  • Decreased activity [ref]

rs9332131, also known as CYP2C9*6

  • Inactive variant.

rs7900194, also known as CYP2C9*8

  • Reduced activity [ref]

rs28371685, also known as CYP2C9*11

  • Reduced activity [ref]

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CYP2C19

There are polymorphisms of CYP2C19 that cause either poor metabolism or ultra-fast metabolism of some drugs.   Approximately 10 – 20% of Asians are poor metabolizers, as are 2 – 5% of people of Caucasian descent.   CYP2C19 enzymes are also involved in breaking down poly-unsaturated fatty acids. CYP2C19 is also involved in activating and breaking down some hormones such as progesterone.

Drug Interactions:
The CYP2C19 enzymes are responsible for the breakdown of several popular drugs including some proton pump inhibitors (Prilosec, Nexium, Prevacid), anti-epileptics, and antiplatelet drugs (Plavix). Pharmacy Times also has an excellent article on CYP2C19 and the drugs it metabolizes.  There is also a list on the Wikipedia page for CYP2D19.

rs12248560, also known as CYP2C19*17

  • Homozygous (TT) ultrafast metabolizer [ref]
  • Decreased risk of breast cancer for carriers of the T allele, and an even bigger decreased risk for T allele carriers who used hormone therapy for 10 years or longer. [ref]
  • One study found that the ultrafast metabolizer: “CYP2C19*17 is likely to cause therapeutic failures in drug treatment with, for example, proton pump inhibitors and antidepressants.” [ref]

rs4244285, also known as CYP2C19*2

  • Poor metabolizer [ref]
  • A study looking at curing H. pylori with omeprazole (Prilosec) and amoxicillin found that poor metabolizers have a much higher cure rate with omeprazole than intermediate and fast metabolizers.  [ref]

rs4986893, also known as CYP2C19*3

  • Poor metabolizer [ref] or loss of function [ref]

rs28399504, also known as CYP2C19*4

  • poor metabolizer [ref]

rs56337013, also known as CYP2C19*5

  • poor metabolizer [ref]

rs72558186, also known as CYP2C19*7

  • poor metabolizer [ref]

rs41291556, also known as CYP2C19*8

  • poor metabolizer [ref]

rs6413438, also known as CYP2C19*10

  • poor metabolizer [ref]

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CYP2D6

There are several important polymorphisms in CYP2D6 which cause either extensive or very poor metabolism – or something in between.  There are both good and bad potential consequences from being a poor or extensive metabolizer.  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.[ref]  Knowing whether you’re a fast or slow metabolizer may make it easier to find the right dosage of certain medications.

Drug Interactions:
The CYP2D6 enzymes metabolize about 25% of pharmaceutical drugs such as SSRI’s, opioids, tamoxifen, Nyquil, and beta blockers.  It also metabolizes serotonin and neurosteroids (pregnanolone, cholesterol, androsterone, etc).  There is a full list of drugs metabolized by CYP2D6 on Wikipedia.

rs3892097, also known as CYP2D6*4

  • Homozygous (TT) is a poor metabolizer.
  • For those taking a beta-blocker that is metabolized through CYP2D6, those with two CYP2D6*4 alleles had lower heart rate leading to an increased risk of bradycardia.  [ref]

rs5030655, also known as CYP2D6*6

  • Homozygous (DD) results in a poor metabolizer phenotype.  [ref]

rs1065852, also known as CYP2D*10

  • Decreased function for homozygous (AA) [ref] [ref]

rs1135824, also known as CYP2D6*3

  • Homozygous (CC) have a non-functioning variant of CYP2D6 [ref]

rs5030867, also known as CYP2D6*7

  • Homozygous has no enzymatic activity. [ref]

rs5030865, also known as CYP2D6*8

  • Homozygous has no enzymatic activity. [ref]

rs28371706, also known as CYP2D6*17

  • Decreased enzyme activity [ref]

rs28371725, also known as CYP2D6*41

  • Decreased enzyme activity [ref]

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CYP2E1

The CYP2E1 gene codes for the enzyme involved in the metabolism of several important drugs as well as the conversion of ethanol to acetaldehyde.  CYP2E1 breaks down or activates several anesthetics, as well as several industrial products including benzene and ethylene glycol.  It is induced by ethanol, and polymorphisms of CYP2E1 are being studied in relation to alcohol induced liver disease. Low levels of alcohol in occasional drinkers are metabolized through the ADH enzyme; higher levels of alcohol induce CYP2E1. [ref]

Dietary Interactions:
While polymorphisms may play a role in increasing or decreasing this enzyme, environmental factors such as alcohol usage may play a larger role for CYP2E1.

Drug Interactions:
There are several anesthetics that are metabolized by CYP2E1 as well as acetaminophen.  List of drugs on Wikipedia.

rs2031920, also known as -1055C>T

  • Higher risk of lung cancer in smokers for TT and CT (small study) [ref]
  • A meta study found a slightly decreased risk of lung cancer [ref]
  • Slightly higher risk of colon cancer (OR=1.16) [ref]

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CYP3A4

CYP3A4 metabolizes about half of the drugs on the market today.  It also is involved in metabolizing some steroids.  A few polymorphisms have been discovered that impact the function of the enzyme, but there are possibly more to be discovered.  Here is an an interesting article from 2013 on the problem of the “missing heritability”.

Dietary Interactions:
Several fruits – grapefruit, noni, pomegranate – are potent inhibitors of CYP3A4.  Eating or drinking these can cause adverse effects on drug metabolism – either increasing the effect of the drug or decreasing the effect.  The effects of grapefruit juice on CYP3A4 enzymes can last for several days.

Drug Interactions:
Pharmacy Times has a good article on drug interactions for CYP3A4 metabolized drugs.  Another long list of drugs metabolized by CYP3A4 is available on Wikipedia.

rs2740574, also known as CYP3A4*1B

  • Significant risk of prostate cancer being aggressive in African American men with G allele [ref]
  • Slightly higher clearance of some CYP3A4 metabolized drugs. [ref]

rs67784355, also known as CYP3A4*11, 1088C>T, T363M

  • decreased enzyme activity [ref]

rs4987161, also known as CYP3A4*17

  • decreased enzyme activity [ref]

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CYP3A5

CYP3A5 is another enzyme that is found in the liver, prostate, and intestines.  It metabolizes several types of drugs as well as testosterone, progesterone, and androstenedione.  There are several polymorphisms that reduce the activity of this enzyme significantly. [ref]

Drug Interactions:
Most drugs listed on the CYP3A4 lists (above) are also metabolized through CYP3A5.  Tacrolimus, which is used in transplant recipients, is one drug for which CYP3A5 polymorphisms are very important.

rs28365083, also known as CYP3A5*2

  • non-functional variant [ref]

rs776746, also known as CYP3A5*3C or CYP3A5*3

  • severe decrease of enzyme activity [ref]
  • non-functioning variant [ref]  note that while this is an uncommon polymorphism for Caucasians, it is very common in other populations

rs41303343, also known as CYP3A5*7

  • non-functioning variant [ref]

rs55817950, also known as CYP3A5*8

  • non-functioning variant [ref]

 
rs28383479, also known as cYP3A5*9

  • non-functioning variant

rs72552791, also known as CYP3A5*11

  • non-functioning variant [ref]

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