GAMT and Creatine

[Tunguska]

Hello,

Sterling's app pointed out these two SNPs for me (rs55776826 was also in the 10% database for the Java app, but didn't show up in snpedia so hadn't noticed it that way):

GAMT rs17851582 A AG +/-
GAMT rs55776826 T TT +/+

No idea what it was until I read http://ghr.nlm.nih.gov/gene/GAMT:

The GAMT gene provides instructions for making the enzyme guanidinoacetate methyltransferase, which is active (expressed) mainly in the liver. This enzyme participates in the two-step production (synthesis) of the compound creatine from the protein building blocks (amino acids) glycine, arginine, and methionine. Specifically, guanidinoacetate methyltransferase controls the second step of this process. In this step, creatine is produced from another compound called guanidinoacetate. Creatine is needed for the body to store and use energy properly. It is involved in providing energy for muscle contraction, and is also important in nervous system functioning.

In addition to its role in creatine synthesis, the guanidinoacetate methyltransferase enzyme is thought to help activate a process called fatty acid oxidation. This process provides an energy source for cells during times of stress when their normal fuel, the simple sugar glucose, is scarce.

So apparently poor GAMT could screw over your natural creatine. Is that correct? Does anyone else have these and looked into them?

These mutations don't seem too popular:

https://opensnp.org/snps/rs17851582 - AG 15%
https://opensnp.org/snps/rs55776826 - TT 2%

This raises the obvious question, should I try supplementing with creatine??? I've always been wary of sports supplements that aren't simple amino acids or whey.

This page describes creatine defiency syndromes: http://www.ncbi.nlm.nih.gov/books/NBK3794/ However I have no idea what would constitute an inefficiency in producing creatine vs a clinical deficiency. Has anyone read the sports research?

 

[Sea]

I haven't looked at this at all yet, but I am heterzygous for both those snps. Interesting for me as I also have a very rare snp on the CPT2 gene which can affect fatty acid processing for energy.

 

[Valentijn]

GAMT rs17851582 A AG +/-
GAMT rs55776826 T TT +/+

rs17851582 isn't pathogenic, even when homozygous, according to http://www.ncbi.nlm.nih.gov/pubmed/12468279 . rs55776826 is also marked as "benign", probably based on the full text of http://www.ncbi.nlm.nih.gov/pubmed/15108290 which I don't have access to. The 2nd one is also not a missense mutation, which usually means little or no impact on the gene.

This raises the obvious question, should I try supplementing with creatine??? I've always been wary of sports supplements that aren't simple amino acids or whey.

I had a pretty horrible reaction to creatine. Whole body swelling, somewhat painful. If trying it be very careful and do a small amount first.

 

[Tunguska]

rs55776826 is also marked as "benign", probably based on the full text of http://www.ncbi.nlm.nih.gov/pubmed/15108290 which I don't have access to. The 2nd one is also not a missense mutation, which usually means little or no impact on the gene.

Thank you. Hope that's accurate (I found the "benign" you mention by searching again; should have checked more of the DBs); would be good news; wasn't too keen on the idea of supplementing creatine for the rest of my life. The 2% and red flag from sterling's app gave the opposite impression. None of this seems particularly reliable!

I had a pretty horrible reaction to creatine. Whole body swelling, somewhat painful. If trying it be very careful and do a small amount first.

Exactly, wary of it because I can do very little exercise at the moment...

 

[Tunguska]

rs55776826 is also marked as "benign", probably based on the full text of http://www.ncbi.nlm.nih.gov/pubmed/15108290 which I don't have access to. The 2nd one is also not a missense mutation, which usually means little or no impact on the gene.

Just wondering also, could you tell me how you translate rs55776826 to those notations they use (e.g., " c.521G>A (exon 5; 1/14 alleles)")? Or know a resource that explains how?

 

[Valentijn]

Just wondering also, could you tell me how you translate rs55776826 to those notations they use (e.g., " c.521G>A (exon 5; 1/14 alleles)")? Or know a resource that explains how?

dbSNP will usually have it listed somewhere for the SNP. It'll list the location of the SNP on the gene, and/or the location of the relevant amino acid on the protein which the gene creates.

I wouldn't recommend trying to figure out which SNP the research is talking about - it's a real pain, and usually doesn't involve ones tested by 23andMe.

 

[Sea]

dbSNP lists these as benign
http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=rs17851582
http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=rs55776826

This one is of more interest (23andme has it as i5002517)
Risk Allele is T
http://www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi?rs=121909272
http://omim.org/entry/601240#0004

Edited to add: Oops, posted without seeing there were more posts after my last one, oh well

 

[Tunguska]

This one is of more interest (23andme has it as i5002517)
Risk Allele is T
http://www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi?rs=121909272
http://omim.org/entry/601240#0004

Got a pass on that one.

Can't report any serious disturbances from a bit of creatine; as usual from supplements didn't notice much at all. If anything interesting happens I suppose I'll post here but doesn't look like this is going to be a smoking gun...

And: Thanks for the replies. As you can probably tell I'm fairly new to this aspect of health.

 

[Critterina]

FWIW, I do NOT have those GAMT mutations, and I HAVE used creatine. Also, my labs occasionally show low creatinine levels (creatinine is the breakdown product of creatine, and low levels are usually associated with a low-protein diet, but not with disease). I had no bad reaction to creatine. I did have a substantial improvement in my athletic performance. I had been doing a route: up one canyon, across a ridge, and down another canyon. It was 5.1 miles and took me 100 minutes (I was counting minutes for a healthy people challenge.). After 2 days of creatine I did it in 88 minutes. After 5 days, I did it in 82 minutes. When you are low in creatine, it does plump up your muscle cells (with fluid), so there may be a slight weight gain, but they work better. My story. Not saying it will be the same for anyone else.