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Interesting MTR Variations

Here's a list of SNPs from 23andMe which have research showing them to be risk factors. Missense mutations are bolded, underlined, and orange.

D919G (A2756G) was particular interesting, as there is a great deal of contradictory information. Much of that comes from cancer research which can a bit problematic due to extra factors coming into play. Most of the research on direct levels of homocysteine says that G is the risky allele. Also, several studies have found that the risk from G is only present, or more pronounced, when combined with other methylation SNPs, most notably G alleles from MTRR missense mutation I22M (A66G).

I'm also doubtful regarding the heartfixer.com explanation that D919G is an upregulation. If it's grabbing up all the available homocysteine, it doesn't make for homocysteine to then be elevated, as is shown in many studies.

T3738 is also a bit of a mystery. I couldn't find much research, but table 3 of http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1626421/ indicates it's significant. However it's not clear which allele they're referring to.

rs1805087....D919G...G....worse with MTRR I22M G alleles
So what is MTR, and why is it important?

MTR is an abbreviation for something really long and annoying, usually called "methionine synthase" now, and is the name of an enzyme and the gene which creates it.

Dysfunction in MTR is related to down-regulation. Because MTR converts homocysteine into methionine, it can cause elevated homocysteine and low methionine levels when it's not functioning properly. It relies upon B12 and MTRR to function (MTRR rececyles the MTR).

B12 might help with MTR dysfunctions. SAMe supplementation also might be necessary, if all else fails and BHMT is also dysfunctional.


Senior Member
Central Illinois, USA
Valentijn, what is the Rs# for MTRR I22M?

Nevermind, just saw the A66G, thx for posting this.

I have many MTR, MTRR polymorphisms (homo and hetero) but I consstently have low homocyctiene so I find the comments interesting. Also have low SamE but high SAH. And the mystery continues :confused: