Genetic variation in the INMT gene strongly impacts the production of trimethylsulfonium in humans.

We previously identified the trimethylsulfonium ion (TMS) in human urine and highlighted its potential as a novel H2S biomarker but observed significant inter-individual variability in its urinary excretion. In this work we investigate the contribution of genetic factors to this variability in a group of European subjects (n = 100) from the BioPersMed cohort. Urinary TMS concentrations displayed two clusters within 5.0-20 nM and 100-400 nM. Genotyping revealed that this clustering is linked to a single nucleotide polymorphism (rs6970396) in the INMT gene, P < 0.001. We found strong contrast in the effects of rs6970396 between TMS and the selenium analogue TMSe which is one of many other detoxification products of the poorly recognized chalcogen-methylation activity of the INMT enzyme. Genetic variability in INMT has wide implications not only for the detoxification of H2S, both inhaled and naturally produced, but also for that of other volatile sulfur compounds in humans which may serve as substrates including xenobiotics.