Posted on February 15, 2020

Researchers at Weill Cornell Medicine-Qatar (WCM-Q) have contributed to an international study which has identified 90 genes that together determine how the human metabolism works to allow the body to rid itself of toxins via the kidneys.

The laboratory of Dr. Karsten Suhre, Director of the Bioinformatics Core at WCM-Q, helped to analyze vast amounts of genetic and metabolic data collected from the 1,600 participants in the study, which was led by the University of Freiburg in Germany. The study involved researchers at institutions in Austria, Germany, the US and Qatar and has been published in Nature Genetics, a world-renowned biomedical research journal. The research sheds light on the genes that influence metabolism and detoxification of the body via the kidneys and urine and whose roles in these processes were previously largely unknown. Given that the human organism metabolizes many thousands of substances that are either ingested or formed within the body itself, these are extremely complex and difficult processes to investigate.

Dr. Suhre said: “All of us at WCM-Q are extremely pleased that we were able to contribute to this important international study, which has given us great new insight into the variation between individuals in the way they metabolize substances.” Researchers are interested in the genetic factors that influence metabolism because they can help them understand why different individuals metabolize the same substances in different ways, which in turn can help explain why some people develop metabolic conditions like kidney stones or type 2 diabetes, or react to medicines differently.

Study director Prof. Dr. Anna Köttgen, Director of the Institute for Genetic Epidemiology at University Medical Center Freiburg, said: “The study results will help in the future to better estimate the individual risk of metabolic diseases. In this way, those affected could adapt their lifestyle in good time.” The study brings another important finding: “Our data underline that certain medications are broken down very differently by different people,” said Köttgen. “In the future, the data could be taken into account in the personal dosage of a drug in order to optimize the effect and avoid side effects.”

The metabolic data used in the study was collected as part of the nationwide German Chronic Kidney Disease (GCKD) study. The data was collected from 1,627 participants with chronic kidney disease and included the concentrations in urine of a total of 1,172 metabolic products, also called metabolites. In the human body, these metabolites are transported back and forth between the individual organs via the bloodstream and excreted via the intestine and kidneys with the help of the liver. By measuring the different concentrations of the metabolites in the urine, doctors can gain information about the body’s metabolic and detoxification performance. The researchers harmonized data from the metabolic concentrations with genetic data to identify 90 genes involved in detoxification-related metabolic activity.

The co-first authors of the study are Dr. Pascal Schlosser, Dr. Yong Li and Dr. Peggy Sekula, all scientists based at the Institute for Genetic Epidemiology at University Medical Center Freiburg. Dr. Schlosser said: “With the help of the genetic variation, we were able to read which enzymes and transport proteins are responsible for the fact that people metabolize, detoxify and excrete substances differently.” “The proteins are primarily active in the intestine, liver and kidneys and often influence how substances are broken down and excreted,” said Dr. Sekula. “We were able to confirm the results in people without kidney disease, so the new insights are also of interest to the general population,” added Dr. Yong Li.

The work of Dr. Suhre was supported by the Biomedical Research Program at Weill Cornell Medicine-Qatar, a program supported by Qatar Foundation. WCM-Q is a member organization of Qatar Foundation.

The study, titled Genetic Studies of Urinary Metabolites Illuminate Mechanisms of Detoxification and Excretion in Humans, can be read in full at https://www.nature.com/articles/s41588-019-0567-8

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