 |
| TMAU - PYROXD2 : read paper |
The paper is by a group of geneticists, none of whom have a history of TMAU research, looking at a few compounds they think is associated with genetic 'positive selection'. In the case of slightly raised TMA levels, They say a single nucleotide polymorphism (SNP) common in those of 'european' ancestry is commonly associated with slightly raised TMA levels.
It may prove productive to relate the TMAu mQTL finding to the rare recessive genetic disorder trimethylaminuria, in which mutations at FMO3 disrupt conversion of TMA to TMAO, resulting in high physiological levels of TMA and an accompanying fish-odour phenotype [47]. Trimethylaminuria cases exhibit relatively low values of the ratio TMAOu/(TMAOu + TMAu), where TMAOu denotes urine TMAO concentration. Subjects in the current study have values of this ratio that are within the range typical of trimethylaminuria controls (Figure S6 and [50]). It will be interesting to investigate the effect, if any, of genetic variation at the TMAu mQTL on TMA levels among trimethylaminuria cases.
The SNP ( rs7072216) is a TT in the PYROXD2 enzyme gene sequence, as opposed to CC (the lowest TMA level type) or TC. It is estimated perhaps 75% of 'european' one T allelle at least. The raised level of TMA is not seemingly expected to be much higher, and still within 'normal' TMA limits, so even if it was correct perhaps it would not play a significant role. At this stage we do not know. The puzzling question is why they did not test FMO3 and how they came to think PYROXD2 would be associated with TMA levels.
It's all a bit too much new information for us, so at the moment it is probably best to not think it plays too signigicant a role, if any, to the understanding that FMO3 deficiency is responsible for genetic TMAU. We are investigating further and will let you know of any updates.
Paper : A Genome-Wide Metabolic QTL Analysis in Europeans Implicates Two Loci Shaped by Recent Positive Selection
![[Facebook Share]](https://lh3.googleusercontent.com/blogger_img_proxy/AEn0k_urMB2y1G-zKf8mNu-cdV_Ixaq-we9lwzo5mkbK9zLpkEXHxixffsAh3wf-0L_ct81GzEk-zbSIZ66exumub8YoDjdB5uo=s0-d){kind=small}
UK 
Spain 
4 comments:
Do we have a consensus yet of what "within normal TMA limits" actually is? I was diagnosed by University of Colorado labs to be within normal limits at 86%; however, I have read other labs considering this percentage to be out of range.
That's a good question. There does not seem to be a consensus and each lab is choosing their own 'normal' ref range. It varies from about 82% to 95% (?). I would say the average consensus might be around 90%. Personally I would regard 86% as below normal.
The problem is that often for 'rare' disorders they use an average minus a few % from samples from a control group to work out a ref range. Probably 'mild' TMAU cases are more common than they realise, and so the average is being drawn down by them.
I think it actually should be where people start to complain of odor, which means it should be set subjectively. Phillips & Shephard in their TMAU article have currently settled for 90% as the mark http://www.ncbi.nlm.nih.gov/books/NBK1103/
My current guess is that a 'real' normal person should be 95%+, probably higher.
Thank you. I agree. University of Colorado and Monell(Dr. Preti) diagnosed me as only a carrier of TMAU.
Did you do the DNA test ? I think one of the problems is that even 'genetic' carriers may sometimes turn out to be 'at risk'. My own perception is that the enzyme needs to be working near perfect to be sure of never having a problem.
An outside chance could be that you are also TT for this new enzyme, which could maybe drag you down say 5%. I have to currently think this is unlikely. This new enzyme variation seems to be most common in white people.