Molecular patterns for subclinical inflammation are associated with complex diseases

C-reactive protein (CRP) is a sensitive marker for subclinical inflammation. In Genome Biology, an international consortium has now reported that epigenetic patterns are associated with CRP and consequently with inflammatory processes. These patterns additionally appear to play a role in cardiovascular and metabolic diseases. DZD scientists were involved in the work conducted within the framework of the consortium.

Acute inflammation generally constitutes a local , transient immune reaction of the human body in response to tissue damage or infections. Various environmental and life-style factors, such as stress, excess weight, and exposure to allergens and chemicals, as well as hereditary factors can, however, lead to subclinical inflammation. This, in turn, has been associated with greater risks for different, often age-related, diseases, such as arteriosclerosis and type 2 diabetes. C-reactive protein (CRP) is a sensitive marker for subclinical inflammatory processes. 

While numerous studies on the genetics of CRP have already been conducted, relatively little is known about epigenetic changes in association with subclinical inflammation. One of the most important epigenetic changes is DNA methylation, in which a methyl group is attached to specific DNA sites. 

Large epigenetics meta-analysis of CRP reveals unknown associations
In order to uncover epigenetic patterns associated with CRP regulation, an international consortium* including scientists from the Helmholtz Zentrum München**has now conducted a large meta-analysis. This analysis combined data on epigenome-wide DNA methylation from more than 10,000 participants in various studies.

"We discovered that numerous DNA methylation sites are associated with inflammatory processes reflected by elevated levels of systemic CRP”, reports Dr. Carola Marzi from the Research Unit for Molecular Epidemiology (AME) at the Helmholtz Zentrum München. Together with colleagues, she is first author of the publication. The associations were independent of numerous risk factors, such as age, sex, smoking and BMI. Some of these methylation sites were additionally associated with the expression of nearby genes and consequently appear to have a direct functional influence on the activity of these genes. Further examinations have indicated that the discovered epigenetic patterns probably also play a role in cardiovascular and metabolic diseases. "Not only do our findings allow new insights into the molecular mechanisms of CRP regulation, they also show possible molecular interfaces between subclinical inflammation and associated diseases," according to Dr. Melanie Waldenberger and Dr. Harald Grallert, both heads of groups in the Research Unit for Molecular Epidemiology (AME).
Further information

* In addition to the Helmholtz Zentrum München, some of the other participants in the work conducted in the framework of the CHARGE Consortium under the aegis of the Erasmus Medical Center were the German Center for Diabetes Research (DZD), the German Diabetes Center (DDZ), the German Center for Cardiovascular Research (DZHK), the Technical University of Munich (TUM), and the German Heart Center Munich (DHM). 

** Some of the Helmholtz Zentrum München participants who worked on the project are: Dr. Carola Marzi, Dr. Harald Grallert and Dr. Melanie Waldenberger (Research Unit for Molecular Epidemiology); Prof. Dr. Annette Peters (Director of the Institute of Epidemiology II), Dr. Katharina Schramm and Dr. Holger Prokisch (Institute of Human Genetics). 

Original publication:
Ligthart S et al (2016): DNA methylation signatures of chronic low-grade inflammation are associated with complex diseases. DOI: 10.1186/s13059-016-1119-5.