GS 224 - Anyone else with GS224 GCH1? - Know how to increase BH4?

Fellowship for kindred spirits.
Post Reply
rep
Contributor
Contributor
Posts: 310
Joined: Tue Oct 14, 2014 1:33 am

GS 224 - Anyone else with GS224 GCH1? - Know how to increase BH4?

Post by rep »

I am growing concerned that part of my heart disease problem could be related to this gs224 GCH1. My genoset lowers BH4 (tetrahydrobiopterin.) Does anyone know anything about this? This and E4 are a bad combination. Promethease assigns this a magnitude of 3.

What medical specialist would I see to test and get to the bottom of this? I don't know where to start.

Does anyone have ideas on how to increase BH4? Apparently BH4 has something to do with nitric oxide (in a bad way) which can cause cardiovascular problems.

From wikipedia:
Since NO production is important in regulation of blood pressure and blood flow, thereby playing a significant role in cardiovascular diseases, tetrahydrobiopterin is a potential therapeutic target. In the endothelial cell lining of blood vessels, endothelial NOS is dependent on tetrahydrobiopterin availability.[8] Increasing tetrahydrobiopterin in endothelial cells by augmenting the levels of the biosynthetic enzyme GTPCH can maintain endothelial NOS function in experimental models of disease states such as diabetes,[9] atherosclerosis, and hypoxic pulmonary hypertension.



I unfortunately have a rare genoset called GS224 http://www.snpedia.com/index.php/Gs224
Among other things it says
You have two copies of a GCH1 variant associated with lower levels of tetrahydrobiopterin (BH4) and total biopterins. BH4 is used in the production of several neurotransmitters, including serotonin and dopamine. While many people carry this with no obvious ill effects, it does seem noteworthy.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2699614/ reports median plasma BH4 levels in patients with this genotype were reduced by approximately 80%. Several potentially serious health issues could result from an 80% reduction in BH4 levels.
There may not be enough BH4 to convert phenylalanine to tyrosine. Therefore, phenylalanine can build up in body tissue and cause health issues (like high blood pressure).
But, now there may not be enough tyrosine, which is needed to create dopamine. And so then there may not be enough dopamine, which can possibly lead to symptoms SIMILAR to conditions like Fibromyalgia and Parkinson’s (but not actually Parkinson’s).
Here is a web page on BH4, or tetrahydrobiopterin http://en.wikipedia.org/wiki/Tetrahydrobiopterin

Nice to finally discover my genetics since I have a history of depression and fibromyalgia. I have started taking methyl B12 and methylfolate (the methylfolate alone can help with depression, I've discovered) but SAMe can supposedly help increase BH4 as well.
http://www.cnsspectrums.com/aspx/articl ... cleid=1267 The article is from a Dr. Stahl, PhD and MD Dr. Stahl is adjunct professor of psychiatry in the Department of Psychiatry at the University of California-San Diego in La Jolla.
Both MTHF and SAMe may therefore impact the regulation of various critical components of monoamine neurotransmitter activity not only by indirect modulation of neurotransmitter synthesis by promoting the synthesis of BH4 enzymatic cofactor, but also by modulating catabolic enzymes, monoamine transporters, and neurotransmitter receptors via methylation and its downstream effects (Figure 5).60-65
ABrain4Me
Senior Contributor
Senior Contributor
Posts: 153
Joined: Thu Oct 23, 2014 5:36 pm

Re: GS 224 - Anyone else with GS224 GCH1? - Know how to increase BH4?

Post by ABrain4Me »

Increasing BH4 is also supposed to help with MAO deficiency-- if you google how to increase BH4, there's some references out there, but I don't see any definitive answers as to whether to supplement with precursors to BH4, or take a BH4 supplement. Perhaps the study will address this issue?
Kim
Contributor
Contributor
Posts: 32
Joined: Fri Feb 20, 2015 10:09 am

Re: GS 224 - Anyone else with GS224 GCH1? - Know how to increase BH4?

Post by Kim »

You can start here http://www.dramyyasko.com/our-unique-ap ... ion-cycle/ for information. It involves methylation and it is very complicated.

One thing I have concluded about the information provided by Promethease is that you cannot always look at each SNP in isolation. If you have one problematic SNP, there may be a backstop somewhere else. For example, I have a MTHFR mutation A1298C (CC) (++) which results in 30% of normal conversion of B-12 to BH4 (and lower levels of neurotransmitters dopamine and serotonin). However, I also have a separate mutation COMT V158M (AA) (++ ) which results in conservation of BH4, so they more or less offset each other.

I think there are very few doctors who understand this stuff. I mostly research it myself and try to figure out what to do. The problem is trying to find a doctor to write a prescription when you think one is needed.

Kim
Kim
Contributor
Contributor
Posts: 32
Joined: Fri Feb 20, 2015 10:09 am

Re: GS 224 - Anyone else with GS224 GCH1? - Know how to increase BH4?

Post by Kim »

I found this group https://groups.yahoo.com/neo/groups/GCH ... sions/info. Apparently this is a separate cycle that affects BH4 independent of the MTHFR cycle? Anyway, they discuss it in this group.

Kim
Heron North
New User
New User
Posts: 2
Joined: Wed Nov 23, 2022 8:54 pm

Re: GS 224 - Anyone else with GS224 GCH1? - Know how to increase BH4?

Post by Heron North »

Metabolic physician. Along with genetic physician
I recently found this in my own full genome and that's the route I'm taking. Zinc, will help. Lots of zinc. Titrate up as necessary. Human breast milk and Royal jelly are good sources of BH4 too
Good luck. I'm trying to find out exactly how rare this is.
NF52
Support Team
Support Team
Posts: 2249
Joined: Tue Oct 25, 2016 9:41 am
Location: Eastern U.S.

Re: GS 224 - Anyone else with GS224 GCH1? - Know how to increase BH4?

Post by NF52 »

rep wrote:
ABrain4Me wrote:
Kim wrote:
Heron North wrote: Wed Nov 23, 2022 8:58 pm Metabolic physician. Along with genetic physician
I recently found this in my own full genome and that's the route I'm taking. Zinc, will help. Lots of zinc. Titrate up as necessary. Human breast milk and Royal jelly are good sources of BH4 too
Good luck. I'm trying to find out exactly how rare this is.
Welcome Heron North,

I'm one of the Moderators and have added links to the three previous posts on this topic, using the quote icon in the upper right of their posts, who will now get an email notification of your helpful reply.

Happy Thanksgiving, if you are in the US!

Nancy
4/4 and still an optimist!
Kmlseattle
Support Team Intern
Support Team Intern
Posts: 46
Joined: Tue Aug 09, 2022 9:46 am

Re: GS 224 - Anyone else with GS224 GCH1? - Know how to increase BH4?

Post by Kmlseattle »

Heron North wrote: Wed Nov 23, 2022 8:58 pm Metabolic physician. Along with genetic physician
I recently found this in my own full genome and that's the route I'm taking. Zinc, will help. Lots of zinc. Titrate up as necessary. Human breast milk and Royal jelly are good sources of BH4 too
Good luck. I'm trying to find out exactly how rare this is.
Welcome, Dr. North.

Thank you so much for sharing your expertise on this forum. Please feel free to post more insights as you see fit. As a welcome intern on this forum I'm here to help you get acquainted to the site and make you aware of some useful resources. The Getting Started page is a great place to start. Also, using the quote button in the upper right corner of a post will ensure the posting user will see you response.

Please feel free to reply with any questions. I wish you the best.

Kathleen
Heron North
New User
New User
Posts: 2
Joined: Wed Nov 23, 2022 8:54 pm

Re: GS 224 - Anyone else with GS224 GCH1? - Know how to increase BH4?

Post by Heron North »

Thank you Kathleen.

I'm not a metabolic physician I was a psychiatrist before I had to give up medicine thanks to this recessive defect but I'm happy to help others on their journey to health.
Post Reply