How we differ in our abilities to detox drugs, toxins, and our own hormones

How we differ in our abilities to detox drugs, toxins, and our own hormones.
Img. by Tareq Saluhuddin

 

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 (pregnenolone, cholesterol, androsterone, etc).

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 of 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.

Knowing whether you’re a fast or slow metabolizer may make it easier to find the right dosage of certain medications.  There is a good list of drugs (substrates) metabolized by CYP2D6 on Wikipedia.

Check your 23andMe results for rs3892097 (v4 only):

  •  TT: CYP2D6*4 – poor metabolizer
  • CT:  typically intermediate metabolizer
  •  CC: extensive metabolizer

 

Check your 23andMe results for rs5030655 (v4 only)

  •  – – : CYP2A6*6 – deletion, poor metabolizer

 

Check your 23andMe results for rs1065852 (v4 only):

  • AA: decreased or non-functioning
  • AG:  somewhat decreased
  • GG: normal

 

Check your 23andMe results for rs1135824 (v4 only):

  •  TT: normal
  • CT:  one copy of CYP2D6*3
  •  CC: two copies of CYP2D6*3, non-functioning

 

Check your 23andMe results for rs5030867 (v4 only):

  •  TT: normal
  • GT:  carrier of one CYP2D6*7 allele
  • GG: carrier of two CYP2D6*7, non-functioning

 

Check your 23andMe results for rs5030656 (v4 only):

  •  I I: normal
  • – I:  carrier of one CYP2D6*9 allele
  • – -: carrier of two CYP2D6*9, non-functioning

 

Check your 23andMe results for rs28371706 (v4 only):

  •  GG: normal
  •  AG:  carrier of one decreased or non-functioning allele
  •   AA: possibly decreased or non-functioning

There are many other, less common variants for CYP2D6. You can check on CYP2D6 on SNPedia for more information.

 

This is part of an ongoing series on the genes involved in detoxification.

Categories: DetoxPhase I Detox

2 Comments

Barbara · May 22, 2018 at 3:53 am

My 23andme test didn’t have many of these CYP genes
on it, but it was done about 4 years ago.
Can you tell me the functioning of these genes? You did
mention the first one, but please confirm on my list.

rsID Minor Allele Genotype Phenotype
rs1065852 A AG +/-
rs1135840 G GG +/+
rs16947 A AG +/-

Also, I have 2 other CYP genes that I am unsure of:

rs1799853 T TT +/+
rs1801272 A AA +/+

I can’t be sure if these +/+ genes are all are always non-functioning
or “bad”. It looks like a lot of non-functioning detox genes.
Is Mercury and other metals part of this group?

Thanks so much. Maybe next month I can donate.

    Debbie Moon · May 22, 2018 at 2:14 pm

    I’m wondering if you perhaps have version 3 results from 23andMe?
    An easy place to look up rs id’s to see links to research studies is http://www.snpedia.com. rs1065852 isn’t linked to a specific CYP2D6 variant that is reduced in function, but it is considered likely to be linked to reduced function. The others that you list on CYP2D6 are ambiguous on their function.

    rs1799853 is a CYP2C9 variant. Here is my article on it: http://www.geneticlifehacks.com/liver-detox-genes-cyp2c9/
    rs1801272 is a CYP2A6 variant. Here is my article on it: http://www.geneticlifehacks.com/liver-detox-genes-cyp2a6/

    The question of whether these variants are ‘bad’ is an interesting one and depends on your perspective and your phase II detoxification. The important thing to know is that they do affect drug metabolism. An easy way to check the drugs that are metabolized through that pathway is to look at the list of ‘substrates’ on the wikipedia page for that specific gene. For example, CYP2C9 metabolizes a lot of the popular NSAIDs including ibuprofen. https://en.wikipedia.org/wiki/CYP2C9

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