CYP21A2

[drob31]

"A defect within the CYP21A2 gene causes a disturbance of the development of the enzyme, which leads to congenital adrenal hyperplasia due to 21-hydroxylase deficiency"

http://en.wikipedia.org/wiki/21-Hydroxylase

Looking at the diagram, I see that this enzyme is responsible for converting progesterone to the step before cortisol or aldosterone.

http://en.wikipedia.org/wiki/21-Hydroxylase#mediaviewer/File:Steroidogenesis.svg

I have a homozygous mutation in rs72547513, although it says it related more to estrogen enzymatic activity, it doesn't specify exactly. Does anyone with adrenal / thyroid / fatigue issues have any notable mutations of this gene?

***EDITED To add reference table***

View attachment 8024

 

[BadBadBear]

I'm confused. Promethius shows CYP1A2 is at rs7254751.

It says CPY21A2 is rs7755898 & some others... Am I looking at the wrong thing? I am interested that CYP21A2 is related to salt wasting, which I definitely experience. And I do have a mutation on rs7755898.

 

[drob31]

There are multiple mutations possible with CYP21A2, from what I understand. How do you experience salt wasting? My blood sodium is usually very high. Do you have water retention from it?

 

[BadBadBear]

Salt wasting for me is lowering blood sodium even with heavy salt loading, water retention - my abdomen gets full of water (I think seeped out into extracellular space), I get extremely thirsty and hyponatremic, my blood pressure drops. My labs always show I am dehydrated, even when I was hyponatremic and drinking 2 gallons a day. I get COLD.

I have been tested for a bunch of things like diabetes insipidus, addisons, etc. and it all comes back negative.

To go to town to shop, I always take 3 bottles of electrolyte drink. I get panicked if I run out, because I get painfully thirsty. I always have a cup of something to sip on in my hand.

It's just the past few years where it's really bad. Before that I needed a lot of fluid, but not so much salt. Now I have to have salt.

 

[Valentijn]

I have a homozygous mutation in rs72547513, although it says it related more to estrogen enzymatic activity, it doesn't specify exactly.

Which version of the SNP do you have? I can't find general prevalence data at dbSNP for it, but my data shows that 12 ME patients and 12 controls all have "AA" for it, so that would seem to be the normal version.

 

[drob31]

I'm AA as well, which nutrihacker says is homozygous.

rs72547513 CYP1A2 C AA: 2/2
Hydroxylation or dealkylation of
xenobiotics, Phase I, metabolize
E2 to 2-hydroxyestradiol
CYP1A2*11 allele with
approximately 5% activity of that
of the CYP1A2 wild type

 

[Valentijn]

I'm AA as well, which nutrihacker says is homozygous.

rs72547513 CYP1A2 C AA: 2/2
Hydroxylation or dealkylation of
xenobiotics, Phase I, metabolize
E2 to 2-hydroxyestradiol
CYP1A2*11 allele with
approximately 5% activity of that
of the CYP1A2 wild type

Either Nutrahacker is wrong or 23andMe is. But based on past experience, Nutrahacker is pretty incompetent, so that's who I'd bet on being the source of misinformation in this case

 

[bertiedog]

"A defect within the CYP21A2 gene causes a disturbance of the development of the enzyme, which leads to congenital adrenal hyperplasia due to 21-hydroxylase deficiency"

http://en.wikipedia.org/wiki/21-Hydroxylase

Looking at the diagram, I see that this enzyme is responsible for converting progesterone to the step before cortisol or aldosterone.

http://en.wikipedia.org/wiki/21-Hydroxylase#mediaviewer/File:Steroidogenesis.svg

I have a homozygous mutation in rs72547513, although it says it related more to estrogen enzymatic activity, it doesn't specify exactly. Does anyone with adrenal / thyroid / fatigue issues have any notable mutations of this gene?

This is really interesting to read because I have virtually adrenal insufficiency and have to take 6.5 mg Prednisolone daily and in the hot weather because I waste salt I run into trouble with things like black spots in front of my eyes, severe sweating and extreme weakness. Half a tab of Fludrocortisone brings me out of it very quickly. I also have Hashimotos but this doesn't cause me any problems now because I take 2 grains of dessicated thyroid every day.

The other interesting thing is I have always had an above level of progesterone even though I am 10 years post menopausal. I have always done very badly on natural progesterone and though I use a small amount of Estrogel daily I don't use any progesterone. This would horrify any doctor because I still have a womb but last year an internal Ultrasound was looking for any endometrial build up but in fact there was none, my levels were practically identical to that of a women of my age (66) who was not on any HRT so I guess this is a result of the progesterone. Probably the next step of conversion to cortisol doesn't happen in my case.

I was mercury poisoned and chelated it out over 10 years ago but perhaps this could account for some of the problems in the pathway which developed over many years through my 30s, 40s and 50s.

One day I would like to get my genetics tested, the only thing holding me back is that I have a fear of illnesses like Alzheimers and wouldn't want to find my genetics were such that I was more likely to get it. Probably silly but that's how I feel.

Pam

 

[drob31]

This is really interesting to read because I have virtually adrenal insufficiency and have to take 6.5 mg Prednisolone daily and in the hot weather because I waste salt I run into trouble with things like black spots in front of my eyes, severe sweating and extreme weakness. Half a tab of Fludrocortisone brings me out of it very quickly. I also have Hashimotos but this doesn't cause me any problems now because I take 2 grains of dessicated thyroid every day.

The other interesting thing is I have always had an above level of progesterone even though I am 10 years post menopausal. I have always done very badly on natural progesterone and though I use a small amount of Estrogel daily I don't use any progesterone. This would horrify any doctor because I still have a womb but last year an internal Ultrasound was looking for any endometrial build up but in fact there was none, my levels were practically identical to that of a women of my age (66) who was not on any HRT so I guess this is a result of the progesterone. Probably the next step of conversion to cortisol doesn't happen in my case.

I was mercury poisoned and chelated it out over 10 years ago but perhaps this could account for some of the problems in the pathway which developed over many years through my 30s, 40s and 50s.

One day I would like to get my genetics tested, the only thing holding me back is that I have a fear of illnesses like Alzheimers and wouldn't want to find my genetics were such that I was more likely to get it. Probably silly but that's how I feel.

Pam

Are you replacing aldosterone? 21-hydroxylase is the only way to get to cortisol or aldosterone, but there is 2 more steps to aldosterone so maybe you have a decrease in another enzyme as well. Have you had any cortisol tests done?

Your poor progesterone conversion would also point to other enzymes, but it's hard to say without getting your gene's checked.

You can actually get your gene test done without getting any information about AD. 23andme doesn't give that info out anymore. So just take the text file, and search it for a gene of interest and check the allele, then you'll never have to discover your AD risks. Actually, it's possible 5-13% of AD are misdiagnosed CJD and possibly vCJD, meaning they are mad cow (BSE). Also, there are many new links to AD and Lyme. I would imagine the genetic risks for AD could be mitigated with proper diet / lifestyle, or greatly reduced. According to my promethese report I have a bunch of risks for it and also a bunch of protective gene's and they all cancel eachother out, leaving me with more questions than answers.

 

[drob31]

Either Nutrahacker is wrong or 23andMe is. But based on past experience, Nutrahacker is pretty incompetent, so that's who I'd bet on being the source of misinformation in this case

So you mean AA is not homozygous, or the info about the gene activity is wrong?

 

[drob31]

Here's an interesting reference table with the gene's relating to the enzymes and the resulting deficiencies:

http://www.questdiagnostics.com/testcenter/testguide.action?dc=CF_CAH

 

[drob31]

From SNPedia:

According to the literature, C is normal and A is rare, however 23andMe data shows that A is more common. At present the consequences remain unclear.

According to the literature, this is the cause of the CYP1A2*11 homozygote which produces 5% Vmax of the normal enzyme level. However 23andMe data shows that A is more common.


http://www.snpedia.com/index.php/Rs72547513(A;A)

 

[Critterina]

Here's an interesting reference table with the gene's relating to the enzymes and the resulting deficiencies:

@drob31 ,
When you post something like this, if you didn't create the table yourself, it's a good practice to give credit (and maybe a hyperlink) to the person or organization that did create it. Some of our inquiring minds will want to see whether it's a reputable source and may be interested in other things that they have to say.
Best,
Crit

 

[drob31]

@drob31 ,
When you post something like this, if you didn't create the table yourself, it's a good practice to give credit (and maybe a hyperlink) to the person or organization that did create it. Some of our inquiring minds will want to see whether it's a reputable source and may be interested in other things that they have to say.
Best,
Crit

Sorry, fixed it for you. I normally quote all my sources--forgot to post the link.

 

[Critterina]

This is really interesting to read because I have virtually adrenal insufficiency and have to take 6.5 mg Prednisolone daily and in the hot weather because I waste salt I run into trouble with things like black spots in front of my eyes, severe sweating and extreme weakness. Half a tab of Fludrocortisone brings me out of it very quickly.

Pam,

Thanks for fixing the link!

Are you sure it's the prednisolone that you're taking for salt wasting and not the Fludrocortisone? I thought the Fludrocortisone was the replacement for the aldosterone (which regulates the electrolytes) and prednisolone was the replacement for the cortisol (that controls inflammation, nausea, extreme weakness, buzzy feeling in limbs, insomnia, and flank pain, and keeps hypoglycemia from occurring every time you go 60-90 minutes without eating - at least that's what prednisone does for me, and I'm on almost the same dose.)

Crit

 

[Valentijn]

So you mean AA is not homozygous, or the info about the gene activity is wrong?

I mean that everyone has AA for that SNP, according to 23andMe. It's not doing anything bad. It's probably a 23andMe universal error (there is at least one other one), or the single study regarding it has a typo (happens frequently). And Nutrahacker hasn't bothered to check that 23andMe gives reliable results for the SNP, despite that it is very easy to do, so they're telling 100% of their customers that they have a mutation which they don't have.

You have the normal version.

 

[bertiedog]

Pam,

Thanks for fixing the link!

Are you sure it's the prednisolone that you're taking for salt wasting and not the Fludrocortisone? I thought the Fludrocortisone was the replacement for the aldosterone (which regulates the electrolytes) and prednisolone was the replacement for the cortisol (that controls inflammation, nausea, extreme weakness, buzzy feeling in limbs, insomnia, and flank pain, and keeps hypoglycemia from occurring every time you go 60-90 minutes without eating - at least that's what prednisone does for me, and I'm on almost the same dose.)

Crit

Absolutely that is exactly how it is with me, Pred for the adrenal insufficiency and blood sugar control plus it so helps with controlling one's reaction to stress (I am quite a chilled person in general) and the occasional Fludro for the salt wasting which is under control most of the time by the Pred but it isn't sufficient with a lot of hot weather despite taking extra Lo Salt for potassium and sodium.

The salt wasting was a lot worse until I got up to the correct amount of Pred for me which is around 6.5 mg so there is also a connection there for sure. At first I had to take 1/2 tab Fludro every day but after a while I didn't need this, the only exception being non-stop hot weather which involves a lot of sweating.

Pam

 

[bertiedog]

Are you replacing aldosterone? 21-hydroxylase is the only way to get to cortisol or aldosterone, but there is 2 more steps to aldosterone so maybe you have a decrease in another enzyme as well. Have you had any cortisol tests done?

Your poor progesterone conversion would also point to other enzymes, but it's hard to say without getting your gene's checked.

You can actually get your gene test done without getting any information about AD. 23andme doesn't give that info out anymore. So just take the text file, and search it for a gene of interest and check the allele, then you'll never have to discover your AD risks. Actually, it's possible 5-13% of AD are misdiagnosed CJD and possibly vCJD, meaning they are mad cow (BSE). Also, there are many new links to AD and Lyme. I would imagine the genetic risks for AD could be mitigated with proper diet / lifestyle, or greatly reduced. According to my promethese report I have a bunch of risks for it and also a bunch of protective gene's and they all cancel eachother out, leaving me with more questions than answers.

Well for me it would seem for the most part taking sufficient Prednisolone (6.5 mg) keeps the aldosterone problem under control as mentioned above except if we get day after day of hot weather when after about 5 or 6 days I will start to get the black spots in front of my eyes and general weakness in my legs which means I have to lie down until the Fludro kicks in.

Thanks for the explanation regarding 23Andme, I will certainly look into it in the very near future because it takes out the guess work. BTW I do have an active Lyme infection an also Ehrlichia and also high levels of various viruses in my blood so there is still a lot going on!

Pam

 

[drob31]

I mean that everyone has AA for that SNP, according to 23andMe. It's not doing anything bad. It's probably a 23andMe universal error (there is at least one other one), or the single study regarding it has a typo (happens frequently). And Nutrahacker hasn't bothered to check that 23andMe gives reliable results for the SNP, despite that it is very easy to do, so they're telling 100% of their customers that they have a mutation which they don't have.

You have the normal version.

Thanks for the clarification. It seems as though these errors can cause us to spin our wheels...

 

[Valentijn]

Thanks for the clarification. It seems as though these errors can cause us to spin our wheels...

The other universal error I've seen was on a Lupus-related gene