Expert comment on the new paper connecting TMA level with PYROXD2 enzyme

The new paper about trimethylamine and enzyme PYROXD2 has been a lot of new information to take in. How significant the paper will be to people with genetic TMAU due to FMO3 deficiency is yet to unfold.

 An expert in TMAU/FMO research, Dr Ian Phillips of Queen Mary University of London, has kindly given us his first observations of the new paper, which is posted below :

Comment by Dr Ian Phillips
Queen Mary University of London

TMA PYROXD2 paper

The paper describes a so-called metabolite quantitative trait locus (mQTL) study. Basically, the researchers looked for associations between the concentrations of various metabolites (small molecules involved in biochemical processes) in urine and plasma and genetic variation (single-nucleotide polymorphisms (SNPs)) from across the entire human genome. They found that ‘high’ concentrations of trimethylamine (TMA) in urine were associated with a T version of a T/C SNP (rs7072216) present in the PYROXD2 gene, which encodes a probable pyridine nucleotide-disulphide oxidoreductase. The gene is on chromosome 10, whereas the FMO3 gene is on chromosome 1.

The results suggest that common variants of the PYROXD2 gene or of a gene that is close to it can affect the amount of TMA excreted in urine. However, the authors state that the 'high' urinary concentrations of TMA associated with TT homozygotes are within the range found in individuals unaffected by primary genetic TMAuria, which is caused by defects in FMO3. Also, the T version of the SNP is present in Europeans at high frequency (70%), which indicates that a relatively high proportion of individuals will be homozygous for the T version of the SNP. Therefore, the SNP is not relevant to primary genetic TMAuria. However, if a person with primary TMAuria is homozygous for the T version of the SNP, the condition might be worse. In addition, it is possible that mild or transient forms of TMAuria, involving common polymorphisms of FMO3, would be exacerbated in people who are homozygous for the T version of the SNP.