How does MTR affect B12?

[cobain_justinsane]

Hello everyone

I'm beginning to think that my b12 levels are as much of an issue as my MTHFR. That's why I'm starting Methylb12 for a while to get my levels up so I don't run into what I think is a methyl trap problem I've had in the past.

I seem to have quite a few mutations in my MTR genes, they are as follows:

MTRR A919G: +/-
MTRR K350A: +/-
MTRR H595Y:+/-
MTRR 11 A644A: +/-

Now I know that the MTR mutations affect the way b12 is used up and recycled in the body, but does anyone know to what degree these mutations cause problems?

Also with these kind of mutations, is there a greater need for b12 supplementation? Much higher doses?

Thanks

 

[Valentijn]

@cobain_justinsane - Do you have some reason to think A919G is relevant? And do you have a rs number for it?

K350A and H595Y are inherited as a bundle, so they're on the same DNA strand, and don't have any additive effect in relation to each other.

A664A +/- is a mild up-regulation, so that's a nice one to have.

As a rule, MTRR mutations have to be homozygous or compound heterozygous to have an impact. You don't have any homozygous there, and because your only relevant heterozygous ones are almost definitely on the same strand, you aren't looking compound heterozygous either.

But if your K350A/H595Y is combined with another serious MTRR missense mutation, you might be compound heterozygous. Here's a list of the other problematic SNPs and alleles from the older 23andMe data when it was testing more:
rs1801394 (G)
rs1532268 (T)
i5003808 (T)

If you're also heterozygous for one of those, there's a 50% that you're compound heterozygous, unless you have 23andMe data from you parents and can figure out for sure.