25 November 2020
Urine analyses inform metabolic processes
Published online 30 January 2020
A study that compared genetic data with urine metabolite concentrations reveals key genes, enzymes and transmembrane transporters involved in metabolism and detoxification processes in humans.
An international research team has identified 90 genes enriched in tissues and cells that influence the metabolism and detoxification of compounds in the human body. Their findings suggest that urine metabolite concentrations can act as a readout of ongoing systemic processes.
The intermediate products of metabolism, known as metabolites, are continually processed by the intestines, liver, blood and kidneys on a cycle of absorption, distribution, metabolism and excretion. Healthy kidneys control the amount of metabolites excreted in urine. Metabolite concentrations are strictly controlled in the blood, but can vary widely in urine. The concentrations of different metabolites in urine therefore carry valuable information about how well the body is processing metabolites.
Anna Köttgen at the University of Freiburg, Germany, and co-workers including a researcher at Weill Cornell Medicine-Qatar in Doha, compared genomic data from 1,627 patients with reduced kidney function with the concentration levels of metabolites in their urine.
“Our results pinpointed 240 relevant genome locations containing 90 genes that are highly expressed in tissues important for metabolite processing,” says Köttgen. “These genes encode proteins that control the generation, transport and breakdown of metabolites.”
The researchers compared the data from the kidney disease patients with data from individuals with normal kidney function and from 450,000 UK Biobank participants. This verified that the 90 genes were linked with metabolism, excretion and detoxification mechanisms. Some of the variations they found indicated pathogenic mechanisms. For example, they found that people with a gene that codes for lower urinary concentrations of the compound phosphethanolamine were more prone to kidney stone disease.
“We also identified key enzymes involved in the metabolism of toxins,” says Köttgen. “The large numbers of known and unknown metabolites we found provides vast scope for future study.” The scientists compiled their data into a comprehensive resource of genetic and molecular targets involved in the body’s metabolic processes that could inform future clinical medicine and pharmaceutical research.
“This study joins previous work in emphasizing that there are many common genetic variants in the human population that associate with important changes in metabolic pathways,” says Amalio Telenti, of the department of integrative structural and computational biology at Scripps Research, California. “Genome-wide association studies of urinary metabolites are a powerful tool that opens doors to improve our understanding of metabolic pathways.”
Schlosser, P. et al. Genetic studies of urinary metabolites illuminate mechanisms of detoxification and excretion in humans. Nat. Gen. https://doi.org/10.1038/s41588-019-0567-8 (2020).