This sounds very interesting (the paper isn't only of interest to the elderly!).
Has anyone had a TCblR (CD320) gene test? Specifically, rs2232780.
(My very old 23andme test reported on two CD320 variants: rs9426 and rs2927707. It's possible different releases contain other CD320 SNPs.)
Transcobalamin receptor gene polymorphisms and mutation in an elderly population
Summary
Background & aims
Cellular uptake of the essential nutrient vitamin B12 (cobalamin) occurs via the transcobalamin receptor (TCblR/CD320), a ubiquitous membrane receptor. Polymorphisms in the receptor exist, though the effect of such variants across patient populations is unknown.
Methods
We determined CD320 genotype in 377 randomly selected elderly individuals.
Results
Three polymorphisms and a codon deletion were identified in the exon 2 region. Haplotype variants had significantly higher holotranscobalamin (holo-TC) values and a higher holo-TC/total cobalamin ratio. TCblR haplotype explained 46% of the variability in holo-TC values.
Conclusions
This has significant implications for the clinical utility of the ‘combined indicator’ of B12 status since it is based on a standard rate of intracellular flux via the TC-Cbl receptor. Modification of the model may be required to account for CD320 haplotype.
I once had genetic testing for a cause of raised MMA - so MMA cblA,B,C,D, types of megaloblastic anaemia, homocystinuria, TCII deficiency etc.
CD320 was on the list, and in "disorder" column: MMA, TCb1R. Nothing was detected there for me.
I had only two comments: MTHFR and MTRR - both having heterozygous variants of uncertain significance.
So nothing useful found for me, but worth trying to find out why MMA remained raised for three years, despite frequent B12 injections. This genetic testing was requested by Adult Inherited Metabolic Diseases consultants in 2018, by which time I was self-injecting EOD.
I had a similar test done. Nothing for CD320 either. However I did have 60+ mutations on 21 of the B12-related genes. 😬 Some were large insertions, a few small deletions, and others single point-mutations. 15 were on CUBN, for Cubilin, which among other things functions as the intestinal absorption of the intrinsic factor-B(12) complex , and reabsorption of various other proteins and carriers.
All were labeled benign but I do wonder if combinations of benign variants can become significant. I found a total of 1 paper suggesting the same thing - an entire family had serious neural tube defect issues and something else B12-related that I've forgotten. They sequenced the genes and they found only benign variants, and nothing else to account for the neural tube issues. Thus they hypothesized that multiple benign variants became pathological. I'm hoping all this new AI research can be applied to these more useful problems.
My suspicion is that we will identify some variants where there is a clear "this variant causes that issue". Followed by some where a variant only causes that issue if another variant is present. And then start to realise that everything is fiendishly complex such that we might never reach satisfactory understanding.
Still there is a reason for all of my sisters' children having autism spectrum problems (in addition to other problems) - and two of my sisters having Grave's disease etc. Genetic links that are not yet understood in any helpful way.
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Antibody to transcobalamin ii causing functional B12 deficiency?
Transcobalamin
Sososo angry with GP
