Stress-sensitivity gene linked to heart attacks, death

Date: Dec-19-2013New research finds that a gene change already linked to stress is also tied

to a 38% higher risk of heart attack or death in people with heart disease.

Researchers from the Duke University Medical Center, Durham, NC, suggest the finding explains

the biology behind why some people may be more susceptible to cardiovascular disease and death.

They report their findings in the online journal PLOS ONE.

The team hopes this means there is a good chance the discovery will lead to drugs and behavior

change treatments that reduce disability and deaths from heart attack.

Senior author Redford B. Williams Jr., professor of medicine and director of the Behavioral

Medicine Research Center at Duke, says:

"We've heard a lot about personalized medicine in cancer, but in cardiovascular disease we are

not nearly as far along in finding the genetic variants that identify people at higher risk. Here

we have a paradigm for the move toward personalized medicine in cardiovascular disease."

Gene variant causes extreme reaction to stress

A genetic variant is a piece of DNA that varies from person to person, like different spellings

of the same word or phrase. A single change in a DNA sequence, known as a single nucleotide

polymorphism (SNP), is where one letter in the genetic code is swapped for another. This is enough

to change how the gene functions, with big or small results.

The new study builds on previous work that found a variation in a DNA sequence in the gene that

makes a serotonin receptor - and causes an extreme reaction to stress. The gene is called

5HTR2C.

In the earlier research, the investigators found that under stress, men with this single SNP

change in their serotonin receptor gene had twice as much of the "stress hormone" cortisol in

their bloodstream than men without the genetic variant.

Cortisol is a hormone secreted in the adrenal gland that helps the body produce a biological

response to situations that trigger negative emotions, for example fear. Among other things, it

increases blood sugar, changes immune response and suppresses systems that are not immediately

required to deal with the perceived stressful event, such as those that deal with digestion,

reproduction and growth.

Lead author Beverly H. Brummett, associate professor of Psychiatry and Behavioral Sciences at

Duke, also explains:

"It has been shown that high cortisol levels are predictive of increased heart disease risk. So

we wanted to examine this more closely."

Carriers at higher risk of heart attack and death

For the study, the team analyzed data gathered from more than 6,100 white heart patients followed

for 6 years, one-third of whom were women. About 13% of the patients had the gene variant that

produced an extreme stress response.

They found that the highest rates of heart attacks and deaths over the follow-up occurred in

patients who carried the gene variant.

Even after they corrected for other possible influencing factors like age, overweight, smoking,

other diseases and heart disease severity, the analysis showed that being a carrier of the gene

variant was linked to a 38% higher risk of heart attack and death.

Dr. Peter Kaufmann is deputy branch chief of the Clinical Applications and Prevention Branch at

the body that funded the study, the National Heart, Lung, and Blood Institute (NHLBI), which is

part of the National Institutes of Health (NIH). He says:

"This research may one day help to identify patients who should be candidates for more intensive

disease prevention and treatment strategies."

He says further studies should now corroborate the findings in a more diverse population.

Speculating on how the gene variant causes the raised cardiovascular risk, the researchers say

it may be something to do with a blood compound called MMP9, an enzyme that rises in line with

cortisol levels.

They suggest MMP9 softens the hard plaques that build up in the linings of arteries, making them

more likely to burst and make clots that can lead to heart attack or death. The team plans to look

further into this.

But in the meantime, Prof. Williams says:

"...what this work suggests already is that we have a found genetic variant that can be easily

identified, so we can begin to develop and test early interventions for those heart patients who

are at high risk of dying or having a heart attack."

In 2011, scientists working on two large international studies, published in Nature

Genetics, discovered 17 new gene

variants tied to coronary heart disease, more than doubling the number of known genetic links

to the disease.

Written by Catharine Paddock PhD

Copyright: Medical News Today

Not to be reproduced without the permission of Medical News Today.

Courtesy: Medical News Today Note: Any medical information available in this news section is not intended as a substitute for informed medical advice and you should not take any action before consulting with a health care professional.