INMT基因的遗传变异强烈影响人类三甲基磺酸的产生

IF 4.2 3区环境科学与生态学 Q2 ENVIRONMENTAL SCIENCES Environmental toxicology and pharmacology Pub Date : 2025-04-01 Epub Date: 2025-02-24 DOI:10.1016/j.etap.2025.104662

Olivia Trummer , Carina Maria Laglstorfer , Christoph W. Haudum , Cornelia Missbrenner , Walter Goessler , Barbara Obermayer-Pietsch , Bassam Lajin

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引用次数: 0

摘要

我们之前在人类尿液中发现了三甲基磺胺离子（TMS），并强调了其作为一种新型H2S生物标志物的潜力，但在其尿液排泄中观察到显著的个体间差异。在这项工作中，我们研究了来自BioPersMed队列的一组欧洲受试者（n = 100）中遗传因素对这种变异性的贡献。尿TMS浓度在5.0-20 nM和100-400 nM范围内呈现两个集群。基因分型显示，这种聚类与INMT基因的单核苷酸多态性（rs6970396）有关，P <； 0.001。我们发现rs6970396在TMS和硒类似物TMSe之间的作用有很强的对比，TMSe是许多其他的解毒产物之一，其解毒产物是INMT酶的低识别的硫甲基化活性。INMT的遗传变异不仅对吸入和自然产生的H2S解毒有广泛的影响，而且对人类体内其他挥发性硫化合物的解毒也有广泛的影响，这些化合物可能作为底物，包括外源性药物。

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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.

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来源期刊

Environmental toxicology and pharmacology 医学-毒理学

CiteScore

7.00

自引率

4.70%

发文量

185

审稿时长

34 days

期刊介绍： Environmental Toxicology and Pharmacology publishes the results of studies concerning toxic and pharmacological effects of (human and veterinary) drugs and of environmental contaminants in animals and man. Areas of special interest are: molecular mechanisms of toxicity, biotransformation and toxicokinetics (including toxicokinetic modelling), molecular, biochemical and physiological mechanisms explaining differences in sensitivity between species and individuals, the characterisation of pathophysiological models and mechanisms involved in the development of effects and the identification of biological markers that can be used to study exposure and effects in man and animals. In addition to full length papers, short communications, full-length reviews and mini-reviews, Environmental Toxicology and Pharmacology will publish in depth assessments of special problem areas. The latter publications may exceed the length of a full length paper three to fourfold. A basic requirement is that the assessments are made under the auspices of international groups of leading experts in the fields concerned. The information examined may either consist of data that were already published, or of new data that were obtained within the framework of collaborative research programmes. Provision is also made for the acceptance of minireviews on (classes of) compounds, toxicities or mechanisms, debating recent advances in rapidly developing fields that fall within the scope of the journal.