德国弗莱堡大学医学院和医学中心Anna Köttgen和Pascal Schlosser共同合作，近期取得重要工作进展。他们研究发现配对代谢组的遗传研究能够揭示血浆和尿液界面的酶促和转运过程。相关研究结果2023年6月5日在线发表于《自然—遗传学》杂志上。

据介绍，肾脏通过清除分子废物同时保留有价值的溶质，在血浆和尿液的界面上发挥作用。配对血浆和尿液代谢组的遗传学研究可以确定潜在的过程。

研究人员对1916种血浆和尿液代谢物进行了全基因组研究，发现1299种显著相关性。单独研究血浆可能会遗漏与40%相关代谢物的关联。研究人员检测到尿液特异性发现，这些发现提供了有关肾脏中代谢物重吸收的信息，如水通道蛋白（AQP）-7介导的甘油转运，以及血浆和尿液中肾脏表达蛋白的不同代谢组足迹，这些代谢组足迹与其定位和功能一致，包括转运蛋白NaDC3（SLC13A3）和ASBT（SLC10A2）。7073种代谢产物-疾病组合的共同遗传决定因素代表了更好地了解代谢性疾病的资源，并揭示了二肽酶1与循环消化酶和高血压的联系。

总之，研究人员表明，将代谢组的遗传学研究扩展到血浆之外，可以对身体隔室界面的过程产生独特的见解。

附：英文原文

Title: Genetic studies of paired metabolomes reveal enzymatic and transport processes at the interface of plasma and urine

Author: Schlosser, Pascal, Scherer, Nora, Grundner-Culemann, Franziska, Monteiro-Martins, Sara, Haug, Stefan, Steinbrenner, Inga, Uluvar, Burula, Wuttke, Matthias, Cheng, Yurong, Ekici, Arif B., Gyimesi, Gergely, Karoly, Edward D., Kotsis, Fruzsina, Mielke, Johanna, Gomez, Maria F., Yu, Bing, Grams, Morgan E., Coresh, Josef, Boerwinkle, Eric, Kttgen, Michael, Kronenberg, Florian, Meiselbach, Heike, Mohney, Robert P., Akilesh, Shreeram, Schmidts, Miriam, Hediger, Matthias A., Schultheiss, Ulla T., Eckardt, Kai-Uwe, Oefner, Peter J., Sekula, Peggy, Li, Yong, Kttgen, Anna

Issue&Volume: 2023-06-05

Abstract: The kidneys operate at the interface of plasma and urine by clearing molecular waste products while retaining valuable solutes. Genetic studies of paired plasma and urine metabolomes may identify underlying processes. We conducted genome-wide studies of 1,916 plasma and urine metabolites and detected 1,299 significant associations. Associations with 40% of implicated metabolites would have been missed by studying plasma alone. We detected urine-specific findings that provide information about metabolite reabsorption in the kidney, such as aquaporin (AQP)-7-mediated glycerol transport, and different metabolomic footprints of kidney-expressed proteins in plasma and urine that are consistent with their localization and function, including the transporters NaDC3 (SLC13A3) and ASBT (SLC10A2). Shared genetic determinants of 7,073 metabolite–disease combinations represent a resource to better understand metabolic diseases and revealed connections of dipeptidase 1 with circulating digestive enzymes and with hypertension. Extending genetic studies of the metabolome beyond plasma yields unique insights into processes at the interface of body compartments. Genome-wide studies of 1,916 plasma and urine metabolites from 5,023 participants of the German Chronic Kidney Disease study provide insights into systemic and kidney-specific enzymatic and transport processes.

DOI: 10.1038/s41588-023-01409-8

Source: https://www.nature.com/articles/s41588-023-01409-8