Abstract：
BACKGROUND: Hydrogen sulfide (H2S) is established as the third gaseous signaling molecule and is known to be overproduced in down syndrome (DS) due to the extra copy of the CBS gene on chromosome 21, which has been suggested to contribute to the clinical manifestation of this condition. We recently discovered trimethylsulfonium (TMS) in human urine and highlighted its potential as a selective methylation metabolite of endogenously produced H2S, but the clinical utility of this novel metabolite has not been previously investigated. We hypothesize that the elevation of H2S production in DS would be reflected by an elevation in the methylation product TMS.
METHODS: To test this hypothesis, a case-control study was performed and the urinary levels of TMS were found to be higher in the DS group (geo. mean 4.5 nM, 95 % CI 2.4-3.9) than in the control (N) group (3.1 nM, 3.5-6.0), p-value 0.01, whereas the commonly used biomarker of hydrogen sulfide, thiosulfate, failed to reflect this alteration in H2S production (15 µM (N) vs. 13 µM (DS), p-value 0.24.
RESULTS: The observed association is in line with the proposed hypothesis and provides first clinical evidence of the utility of TMS as a novel and more sensitive biomarker for the endogenous production of the third gaseous signaling molecule than the conventionally used biomarker thiosulfate, which is heavily dependent on bacterial hydrogen sulfide production.
CONCLUSIONS: This work shows that TMS must be explored in clinical conditions where altered metabolism of hydrogen sulfide is implicated.
METHODS: To test this hypothesis, a case-control study was performed and the urinary levels of TMS were found to be higher in the DS group (geo. mean 4.5 nM, 95 % CI 2.4-3.9) than in the control (N) group (3.1 nM, 3.5-6.0), p-value 0.01, whereas the commonly used biomarker of hydrogen sulfide, thiosulfate, failed to reflect this alteration in H2S production (15 µM (N) vs. 13 µM (DS), p-value 0.24.
RESULTS: The observed association is in line with the proposed hypothesis and provides first clinical evidence of the utility of TMS as a novel and more sensitive biomarker for the endogenous production of the third gaseous signaling molecule than the conventionally used biomarker thiosulfate, which is heavily dependent on bacterial hydrogen sulfide production.
CONCLUSIONS: This work shows that TMS must be explored in clinical conditions where altered metabolism of hydrogen sulfide is implicated.
摘要：
背景：硫化氢（H2S）被确定为第三种气态信号分子，并且已知由于21号染色体上CBS基因的额外拷贝而在唐氏综合征（DS）中过度产生，这已被认为有助于这种情况的临床表现。我们最近在人类尿液中发现了三甲基锍（TMS），并强调了其作为内源性产生的H2S的选择性甲基化代谢产物的潜力。但是这种新的代谢产物的临床应用尚未得到研究。我们假设DS中H2S产生的升高将通过甲基化产物TMS的升高来反映。
方法：为了检验这一假设，进行了一项病例对照研究，发现DS组的TMS尿水平较高（geo.mean4.5nM,95%CI2.4-3.9)比对照组（3.1nM，3.5-6.0),p值0.01，而常用的生物标志物硫化氢，硫代硫酸盐，未能反映H2S产量的这一变化(15µM(N)与13µM(DS)，p值0.24。
结果：观察到的关联与提出的假设一致，并提供了第一个临床证据，证明TMS作为一种新型和更敏感的生物标志物，用于内源性产生第三种气体信号分子，而不是常规使用的生物标志物硫代硫酸盐，严重依赖细菌硫化氢的产生。
结论：这项工作表明，必须在涉及硫化氢代谢改变的临床条件下探索TMS。
方法：为了检验这一假设，进行了一项病例对照研究，发现DS组的TMS尿水平较高（geo.mean4.5nM,95%CI2.4-3.9)比对照组（3.1nM，3.5-6.0),p值0.01，而常用的生物标志物硫化氢，硫代硫酸盐，未能反映H2S产量的这一变化(15µM(N)与13µM(DS)，p值0.24。
结果：观察到的关联与提出的假设一致，并提供了第一个临床证据，证明TMS作为一种新型和更敏感的生物标志物，用于内源性产生第三种气体信号分子，而不是常规使用的生物标志物硫代硫酸盐，严重依赖细菌硫化氢的产生。
结论：这项工作表明，必须在涉及硫化氢代谢改变的临床条件下探索TMS。
