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How Do Individuals React to Metabolic Stress? - Genetic Variation in Metabolism Identified

Metabolic diseases – in particular the increasingly prevalent type 2 diabetes – are caused by a complex interaction between genetic disposition and unfavorable lifestyle, above all unbalanced diet and too little physical exercise. Researchers at the Helmholtz Zentrum München have now for the first time been able to show a relationship between the genetic make-up of an individual and differences in his/her metabolism.

The team of Professor Karsten Suhre of the Institute for Bioinformatics and Systems Biology at the Helmholtz Zentrum München and the Ludwig-Maximilians Universität München (LMU) and Dr. Christian Gieger and Thomas Illig of the Institute for Epidemiology in cooperation with the Innsbruck company Biocrates Life Sciences AG determined the blood test results of several hundred metabolites synchronously with more than 100 000 DNA variants (SNPs) of 284 adult test subjects.

Their research was based on blood samples of participants of the population-based KORA study (Kooperative Gesundheitsforschung in der Region Augsburg [Cooperative Health Research in the Region of Augsburg] which is headed by Professor H.-Erich Wichmann).

By combining comprehensive genetic data with metabolite data, the scientists identified genetic variants (SNPs) in several genes that code for enzymes which perform important tasks in the body’s metabolism of lipids, sugars and carbohydrates. Individuals who differ from each other through such gene variants exhibit at the same time very different activity of the affected enzymes, which is apparent in the different metabolite concentrations in the serum. Simply expressed, the individuals in the study had different metabolic patterns (metabotypes) due to genetic factors.

“These are at least partly comparable to the different varieties of hair color which are due to genetic variations,” Karsten Suhre said. Redheads react more sensitively to sunlight than dark-haired individuals do. It may be similar with the genetic variations identified here, which are responsible for the different metabotypes.

While one group is able to react relatively robustly to “metabolic stress“, e.g. in the form of a short-term nutritional deficiency or a high-fat diet, another group may have more or less pronounced physical impairments, the precise extent of which can now be ascertained in follow-up studies. “For example, differences in hair color are apparent to the observer at first glance. However, in the case of metabolism it takes much more effort to identify the role which the respective gene variant plays in the metabolism of the affected person,“ Karsten Suhre explained.

In this study, by means of a genome-wide analysis, the cross-institutional working group succeeded for the first time in profiling a number of such relationships. The identification of such genetically induced variations in the metabolism can be utilized in the future to predict risks with respect to certain medical phenotypes, possible reactions to medical treatment, nutritional or environmental influences – a first step towards personalized medicine and nutrition, based on a combination of a genetic and metabolic characterization of the patients.

Michael van den Heuvel | alfa
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