Scientists discover genetic link between misery and death

Washington, Feb 25 (ANI): UCLA researchers have found the genetic link between misery and death.

The new study has also discovered a specific genetic variation in some people that apparently disconnects that link, rendering them more biologically tough to face adversity.

Steven Cole, a member of the UCLA Cousins Center for Psychoneuroimmunology and an associate professor of medicine in the division of hematology-oncology, and his team have developed a unique strategy for finding and confirming gene-environment interactions to more efficiently investigate what he calls the "genetic haystack."

Cole and his team used an approach that blends computational, in vivo and epidemiological studies to look at specific groups of proteins known as transcription factors, which regulate gene activity and mediate environmental influences on gene expression by binding to specific DNA sequences. These sequences differ within the population and may have an effect on a gene's sensitivity to environmental activation.

Particularly, Cole analysed transcription factor binding sequences in a gene called IL6, a molecule that is known to cause inflammation in the body and that contributes to cardiovascular disease, neurodegeneration and some types of cancer.

Cole said: "The IL6 gene controls immune responses but can also serve as 'fertilizer' for cardiovascular disease and certain kinds of cancer.

"Our studies were able to trace a biochemical pathway through which adverse life circumstances - fight-or-flight stress responses - can activate the IL6 gene.

"We also identified the specific genetic sequence in this gene that serves as a target of that signaling pathway, and we discovered that a well-known variation in that sequence can block that path and disconnect IL6 responses from the effects of stress."

To confirm the biochemical link between misery and death, and the genetic variation that breaks it, the scientists turned to epidemiological studies to prove that carriers of that specific enetic variation were less vulnerable to death due to inflammation-related mortality causes under adverse social-environmental conditions.

They discovered that people with the most common type of the IL6 gene demonstrated an increased risk of death for approximately 11 years after they had been exposed to adverse life events that were strong enough to trigger depression. However, people with the rarer variant of the IL6 gene appeared to be immune to those effects and showed no increase in mortality risk in the aftermath of significant life adversity.

This unique method of discovery - using computer modelling and then confirming genetic relationships using test-tube biochemistry, experimental stress studies and human genetic epidemiology - could speed the discovery of such gene and environmental relationships, according to the researchers.

Cole, who is also a member of UCLA's Jonsson Comprehensive Cancer Center and UCLA's Molecular Biology Institute, said: "Right now, we have to hunt down genetic influences on health through blind searches of huge databases, and the results from that approach have not yielded as much as expected," Cole said. "This study suggests that we can use computer modeling to discover gene-environment interactions, then confirm them, in order to focus our search more efficiently and hopefully speed the discovery process.

"This opens a new era in which we can begin to understand the influence of adversity on physical health by modeling the basic biology that allows the world outside us to influence the molecular processes going on inside our cells."

The research has been published online in the Proceedings of the National Academy of Sciences. (ANI)