Interesting MTRR Variations

[Valentijn]

Here's a list of 23andMe SNPs which have research showing some malfunction, except for L333V which is rare as GG but has no research associated with it. Missense mutations are underlined, bolded, and orange.

I'm listing the risk of A664A backwards of what Yasko does - this study (table 4), shows that it's looking at risk associated with the minor allele (A). Because the hazard ratio is less than 1, that means that A is protective, not causative.

rsID.........NAME....RISK...ETC
rs1801394....A66G....G
rs3776467....G827A...G
rs1532268....S175L...TT
rs7703033....G1515A..A
rs10064631...L333V...GG?..rare
rs162036.....K350R...G
rs2287780....R415C...T
rs137853062..S454L...T....i5003808
rs162049.....A95G....G
rs10380......H595Y...T
rs1802059....A664A...GG...A is protective
rs9332.......G541A...A

 

[Little Bluestem]

Where is your summary of what this gene does? Some of us need that.

 

[Valentijn]

Where is your summary of what this gene does? Some of us need that.

MTRR is the abbreviation for a gene called "5-methyltetrahydrofolate-homocysteine methyltransferase reductase" or "methionine synthase reductase"(MSR), and the enzyme which it creates. Basically after another enzyme, methionine synthase (MTR), loses its B12 and stops functioning, MTRR remethylates the MTR so that MTR can get back to work.

Problems with MTRR can result in elevated homocysteine and low methionine. B12 supplementation is probably helpful.

PS - Sorry for the delay, it took me all night to type out the full name of MTRR

 

[Lynn_M]

Valentijn,
In the study you referenced, allele A of rs1802059, MTRR A664A, has an adjusted hazard ratio of 0.42, and because that is less than 1, you said A is protective. I have no argument with that. It should be mentioned that in this particular research protective meant there was less risk associated with that SNP for acute cyclosporine toxicity in kidney transplant patients.

However, in that same study, Table 4 shows allele A of rs1532268, MTRR S175L, has an adjusted hazard ratio of 0.43. So by that same logic, A, the minor allele, should be considered protective. Yet you considered TT to be the risk allele. I don't understand your basis for that.

 

[Valentijn]

However, in that same study, Table 4 shows allele A of rs1532268, MTRR S175L, has an adjusted hazard ratio of 0.43. So by that same logic, A, the minor allele, should be considered protective. Yet you considered TT to be the risk allele. I don't understand your basis for that.

More applicable research for that SNP is available at http://www.ncbi.nlm.nih.gov/pubmed/12416982?dopt=Abstract which indicates that TT results in MTRR having 1/3 or 1/4 of the usual effectiveness in repairing MTR, and is associated with heart defects.

Yes, it's all a bit contradictory, but that's often the case, especially with smaller effect sizes or when a huge number of SNPs are being tested. Also, the other study is looking at disease risk in patients, and comparing it to SNP prevalence rate, which is a lot more subject to false-positive (coincidental) results. Whereas this study I've cited in this post is directly looking at the actual activity of substance produced by the gene.

So this study is the more persuasive one regarding S175L, and the evidence for A664G is pretty weak in general.