• Welcome to Phoenix Rising!

    Created in 2008, Phoenix Rising is the largest and oldest forum dedicated to furthering the understanding of and finding treatments for complex chronic illnesses such as chronic fatigue syndrome (ME/CFS), fibromyalgia (FM), long COVID, postural orthostatic tachycardia syndrome (POTS), mast cell activation syndrome (MCAS), and allied diseases.

    To become a member, simply click the Register button at the top right.

Question about detox genes which are homozygous (+/+)

jason30

Senior Member
Messages
511
Location
Europe
Hi,

I have the following homozygous mutations (+/+):
CYP1A2*1F +/+
CYP1B1 L432V
CYP1B1 N453S
CYP1B1 T241A
CYP2B6 T23499C
CYP2C19 T98C
CYP2D6 C186G
CYP2D6 T130G
CYP2D6*2 S486T
CYP3A4*16 T185S

They are all connected to cytochrome p450 phase 1.
I am trying to learn more about it, so any information about these are welcome.

I wonder, for example CYP1B1, do I have an increased or decreased activity of CYP1B1 when you have +/+ homozygous?
https://www.selfdecode.com/gene/CYP1b1/#experiments_decrease

Thanks.
 

alicec

Senior Member
Messages
1,572
Location
Australia
There are many CYP enzymes with varying roles in phase I detox and other activities such as synthesis and catabolism of steroids. They are divided into families and subfamilies with about a dozen members of families 1,2,and 3 being responsible for drug metabolism.

Here is a review of CYP enzymes and drug metabolism. It is fairly heavy going but you can just look at the figures and tables. Fig 1 shows the contributions of the differents CYP enzymes to drug metabolism and Table 1 lists CYP genetic variants known to affect drug metabolism.

You can compare your SNPs with this list.

I wonder, for example CYP1B1, do I have an increased or decreased activity of CYP1B1 when you have +/+ homozygous?

This entirely depends on the SNPs. They may have no effect at all - you need to look at the research for your particular SNPs and you need to understand that the presence of a variant often means nothing whatsoever.

The Self-decode entry you link is mainly talking about associations of SNPs and various conditions. Association doesn't mean causation and many of these SNP association studies are not very reliable. It depends how big the study was and how robust the statistics.

Here is the OMIM entry for CYP1B1. The only known disease caused by CYP1B1 variants is early onset glaucoma and the only robust disease association is with breast cancer.

ETA Variation in activity of an enzyme such as described by Self-decode isn't only attributable to SNPs in the gene for the enzyme. Changes in other genes or non-genetic factors can also be important.
 
Last edited:

jason30

Senior Member
Messages
511
Location
Europe
Sorry for the late respons, a virus kept me busy for 3 weeks!

Thank you for thinking along and the info @alicec , I've become a little wiser. :)

I see often that they talk about 'genetically impaired CYP2B6'.
When does someone have an impaired CYP2B6? Is that equal to a homozygous mutation (+/+)?

Thanks again.
 

alicec

Senior Member
Messages
1,572
Location
Australia
When does someone have an impaired CYP2B6?

A genetically impaired CYP2B6 is the result of a mutation in DNA that affects the structure or production of the protein product so that little or no enzyme activity is present.

Table I in the paper I linked above list DNA changes in CYP2B6 known to result in a defective enzyme. OMIM.org would also have an entry which you can find by just inserting CYP2B6 in the search box.

Is that equal to a homozygous mutation (+/+)?

Not necessarily, it entirely depends on which +/+ SNP.

As I have already said, the presence of a variant often means nothing at all. A few may have an effect. You need to look at research or research summaries such as the ones I have linked to find out which variants actually alter the activity of the enzyme and to what extent.
 

wastwater

Senior Member
Messages
1,267
Location
uk
CYP1B1 is connected to FOXC1 and I can confirm through lived experience it can cause breast cancer in women and early onset glaucoma
Maybe FOXC1 is important from there it effects HSP6A FOXO1A among others
FOXO1A for IDO2
Also EBV effects FOXO1A and that effects FOXP3 for T cells

Could it all be due to FOXC1 dosage