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DNA Methylation Plays Important Role in Human Metabolism

Biological functions of organisms are also controlled by higher-­level regulatory mechanisms, which are grouped under the term epigenetics. Epigenetic modifications, such as methylation of protein components of chromosomes, can help to determine the fate of genes and are passed on to some extent even to subsequent generations.

Aging processes, but also environmental and lifestyle factors such as smoking or diet cause biochemical modifications in the DNA during the course of a lifetime. This can lead to methylation of the DNA components, whereby methyl groups are added without changing the actual DNA sequence. These processes, known as epigenetic changes, can impact gene function. Scientists of the Institute of Genetic Epidemiology and the Research Unit Molecular Epidemiology carried out an epigenome-wide association study to determine if there are any associations – and if so which associations – between epigenetic processes and health consequences for the metabolism. For this purpose, the team led by Christian Gieger and Melanie Waldenberger in collaboration with Karsten Suhre from Weill Cornell Medical College in Qatar analyzed blood samples of more than 1800 participants of the KORA study (Cooperative Health Research in the Augsburg Region). In the samples they analyzed more than 457 000 positions in the DNA to detect epigenetic alterations and compared these with concentrations of 649 different metabolites. The analysis showed that methylation of 28 DNA segments changed a number of important metabolic processes.
In the respective DNA regions, already known disease-associated genes were also found, such as the gene TXNIP, which regulates glucose metabolism and is associated with the development of diabetes mellitus. Consistent with this finding, altered concentrations of metabolites of the lipid and glucose metabolism were found in the methylated TXNIP. Moreover, genes that can be biochemically altered by smoking affect different metabolic activities.
The study provides new insights into how lifestyle factors can influence the metabolism through DNA alterations. The results will be used to develop new diagnostic and therapeutic approaches for lifestyle-related diseases.

Biological functions of organisms are also controlled by higher-­level regulatory mechanisms, which are grouped under the term epigenetics. Epigenetic modifications, such as methylation of protein components of chromosomes, can help to determine the fate of genes and are passed on to some extent even to subsequent generations.



Schematic view of processes through which genetic variance and CpG methylation can be influenced in the metabolism. Possible feedback reactions are depicted by dashed lines. Source: HMGU