How many cigarettes a day a person smokes – and how hard it is for them to quit – is at least partly dependent on the CYP2A6 gene.
This article explains the function of the CYP2A6 gene, which is part of the CYP450 family of enzymes tasked with breaking down and eliminating substances in the body. Additionally, we will explore the genetic variants (check your genetic raw data) in the CYP2A6 gene and then cover ways to speed up or slow down the enzyme.
CYP2A6 is part of the CYP450 family of genes that code for detoxification enzymes. (Learn more about other detoxification genes.)
The CYP2A6 enzyme is involved in the break down (metabolism) of:
- tegafur (cancer drug)
- Letrozole (cancer drug)
- Efavirenz (antiretroviral)
- Artemisinin (antimalarial)
- valproic acid (antiepileptic, bipolar, migraine med)
- Pilocarpine (glaucoma and dry mouth)
Note that some drugs are metabolized through more than one CYP enzyme.
The estrogen hormone, estradiol, causes higher CYP2A6 activity, and women usually have a somewhat higher activity of this enzyme.[ref]
We don’t just produce CYP2A6 to break down chemicals and drugs. In the body, the CYP2A6 enzyme also breaks down retinoic acid and some steroid compounds.[ref]
While other enzymes can also break down nicotine, the primary way that your body metabolizes it (breaks it down) is through hepatic CYP2A6 (70–80%). Also important to note is that the major metabolite of nicotine, called cotinine, is exclusively metabolized by the CYP2A6 enzyme.[ref] So the CYP2A6 enzyme is responsible for two steps in the body’s process of getting rid of nicotine.
When it comes to smoking, the CYP2A6 genetic variants impact the speed at which nicotine is metabolized.
Researchers link genetic variants of CYP2A6 that cause decreased enzyme activity with a lower level of dependence in smokers, making it easier for them to quit. Basically, the slower CYP2A6 variants make the effects of nicotine last longer, thus reducing the number of cigarettes smoked.
On the other hand, people with increased CYP2A6 enzyme activity have an enhanced metabolism of nicotine and are likely to smoke more cigarettes per day.[ref]
Genetic Variants – CYP2A6:
The CYP2A6 gene shows a lot of variation among individuals. These variants are common polymorphisms for which the data is available in 23andMe or AncestryDNA.
In general, research shows that people with reduced (or slow) CYP2A6 activity are more likely to quit smoking. Among smokers, slow CYP2A6 activity is linked with smoking fewer cigarettes per day.[ref][ref]
Check your genetic data for rs1801272 (23andMe v4 ; AncestryDNA):
Members: Your genotype for rs1801272 is —.
*note: listed in the plus orientation to match 23andMe, AncestryDNA data
Check your genetic data for rs5031017 (23andMe v4 only):
- A/A: CYP2A6*5 – non-functioning variant[ref]
- A/C: One CYP2A6*5 allele, reduced activity
- C/C: typical
Members: Your genotype for rs5031017 is —.
Check your genetic data for rs5031016 (23andMe v4, v5; AncestryDNA):
- G/G: CYP2A6*7 – non-functioning variant[ref]
- A/G: One CYP2A6*7 allele, reduced activity
- A/A: typical
Members: Your genotype for rs5031016 is —.
Check your genetic data for rs28399444 (23andMe v4 only):
- DD or -/- : CYP2A6*20 – non-functioning variant[ref]
- DI or -/TT: One CYP2A6*20 allele, reduced activity
- II or TT / TT: typical
Members: Your genotype for rs28399444 is —.
Interaction with POR Gene Variants:
Another gene, POR (P450 cytochrome oxidoreductase), codes for an enzyme that can also alter the activity of other CYP450 enzymes.
Check your genetic data for rs1057868 (23andMe v4, v5; AncestryDNA):
- C/C: normal enzyme activity
- C/T: normal enzyme activity
- T/T: may increase CYP2A6 enzyme activity in people with normal CYP2A6 variants[ref]
Members: Your genotype for rs1057868 is —.
Genetic variants that increase CYP2A6 activity are associated with increased smoking risk.
Check your genetic data for rs28399453 (23andMe v4 only)
- G/G: typical
- A/G: increased CYP2A6 activity
- A/A: increased CYP2A6 activity[ref]
Members: Your genotype for rs28399453 is —.
Grapefruit juice contains a substance that inhibits CYP2A6 enzyme activity. So be careful – especially if you have a slow variant of the gene – with combining grapefruit juice with any drug that is metabolized by CYP2A6.[ref]
Higher doses of cinnamon, such as you might take to regulate blood sugar levels, have been shown to inhibit CYP2A6 enzyme activity.[ref] If you are a slower CYP2A6 metabolizer, you may want to be careful about too much cinnamon if you also take one of the medications listed below.
More Effective for Quitting Smoking:
Bupropion is a prescription-based smoking cessation drug. Clinical trials show that for people with slow CYP2A6 function (e.g. variants above), bupropion is not statistically more effective than placebo. But… for people with normal (faster) CYP2A6 function, bupropion is 3 times more effective than placebo.
Likewise, Varenicline, a smoking cessation drug targeting the nicotine receptor, was much more effective than nicotine patches for normal (faster) CYP2A6 functioning people, while people with lower enzyme function were just as easily able to quick with a nicotine patch as with Varenicline.[ref]
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Related Articles and Topics:
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.
Statins and Muscle Pain: Genes that impact myopathy
Statins are one of the most prescribed medications in the world. One side effect of statins is myopathy, or muscle pain and weakness. Your genetic variants are important in whether you are likely to have side effects from statins.
CYP1A1: Estrogen, hydrocarbons, air pollution
This phase I detoxification gene is important in the breakdown of the hydrocarbons produced in smoke and air pollution. It also affects the metabolism of estrogen.
Originally published 6/2/2015. Updated 6/2020
Debbie Moon is the founder of Genetic Lifehacks. Fascinated by the connections between genes, diet, and health, her goal is to help you understand how to apply genetics to your diet and lifestyle decisions. Debbie has a BS in engineering and an MSc in biological sciences from Clemson University. Debbie combines an engineering mindset with a biological systems approach to help you understand how genetic differences impact your optimal health.