Featured Research

from universities, journals, and other organizations

Gene Variation In Immune System Cells Lowers Heart Disease Risk

Date:
April 16, 2003
Source:
NIH/National Institute Of Allergy And Infectious Diseases
Summary:
In a serendipitous spin-off of HIV/AIDS research, scientists at the National Institute of Allergy and Infectious Diseases (NIAID) and colleagues have found strong evidence that a genetic variation affecting immune system cells protects against heart disease.

In a serendipitous spin-off of HIV/AIDS research, scientists at the National Institute of Allergy and Infectious Diseases (NIAID) and colleagues have found strong evidence that a genetic variation affecting immune system cells protects against heart disease. Details of the work, which also provides further evidence for the role of inflammation in heart disease, will appear in the April 15 issue of the Journal of Clinical Investigation.

Related Articles


"This work demonstrates how NIAID's commitment to HIV/AIDS research can provide insights into the mechanisms of other diseases," says NIAID director Anthony S. Fauci, M.D. "The money spent on this research, so important to the millions of people around the world infected with HIV, also results in wider ranging benefits."

"The genetic variation we studied has a positive and protective effect against atherosclerosis. This effect is similar in magnitude, though opposite in value, to known negative risk factors such as diabetes and smoking. In other words, as bad as the negative risk factors are bad, this factor is good," says senior study author Philip M. Murphy, M.D. "In addition, the study may help explain part of the hereditary component of heart disease, establishing not only a genetic association but also giving evidence for a biological cause."

Dr. Murphy and colleague David McDermott, M.D., have been studying several different receptor molecules on the surface of immune system cells to understand the role these molecules play in HIV infection. Recently, they concentrated on a receptor molecule called CX3CR1, which binds to a signaling molecule called fractalkine. Fractalkine, sometimes found in atherosclerotic vessels, attracts immune system cells bearing CX3CR1 and helps them attach to infected or diseased tissue. The NIAID scientists speculated that in atherosclerotic tissues, fractalkine might attract immune system cells and encourage them to bind to the walls of blood vessels, thereby triggering inflammation and plaque formation that eventually blocks the vessel.

Working with colleagues at the National Heart, Lung, and Blood Institute (NHLBI), the NIAID scientists performed a detailed genetic analysis of the offspring cohort of the famous Framingham Heart Study. In this population of more than 1,800 individuals, the researchers showed that a genetic variant of the CX3CR1 receptor, called CX3CR1-M280, was associated with a significantly lower risk of heart disease, even after adjusting for age, sex and negative risk factors such as cigarette smoking, high cholesterol, diabetes and hypertension.

Because previous studies established that mice lacking the CX3CR1 receptor also had reduced risk of heart disease, the NIAID scientists speculated that the human CX3CR1 variant might not function well. A battery of laboratory tests proved that this was in fact the case: When compared with "normal" CX3CR1, the M280 variant did not bind well to fractalkine or respond to its attracting signal. The finding suggests that people with the M280 variation are less susceptible to arterial inflammation triggered by immune system cells. So far, there is no evidence that the variant causes any ill effects. Duke University Medical Center researcher Dhavalkumar D. Patel, M.D., Ph.D., collaborated with the NIAID team on this part of the study.

"The strength of this study is that it examined an entire population, not just one group of people already at risk for heart disease," explains Dr. McDermott. "When you examine an entire population, you are less likely to overestimate the significance of the risk factor you are studying." The collaboration of Dr. Christopher O'Donnell and colleagues at NHLBI and the Framingham Heart Study were invaluable to this effort, Dr. McDermott notes.

"This study provides a great example of how the Framingham genetic database can contribute to multidisciplinary collaboration," says NHLBI Director Claude Lenfant, M.D. "This database is available for use by researchers and provides important and novel information that may one day translate to patient care."

By establishing a connection between a specific cell receptor, CX3CR1, and atherosclerosis, the researchers have spotlighted CX3CR1 as a potential target for drugs that block its action. "Even though scientists have the entire sequenced human genome to examine, it is still extremely difficult to find drug targets unless you have robust cohorts like this one to test," notes Dr. Murphy.

The M280 variant gene differs from the usual CX3CR1 gene at two key points. Next, the NIAID researchers would like to discover if one, the other, or both of these changes cause the variant molecule to function differently. In addition, the researchers would like to follow up on studies in mice that suggest CX3CR1 plays a role in other inflammatory diseases such as stroke or the kidney disease glomerulonephritis.

###NIAID is a component of the National Institutes of Health (NIH), an agency of the Department of Health and Human Services. NIAID supports basic and applied research to prevent, diagnose, and treat infectious and immune-mediated illnesses, including HIV/AIDS and other sexually transmitted diseases, illness from potential agents of bioterrorism, tuberculosis, malaria, autoimmune disorders, asthma and allergies.

Reference: D McDermott et al. Chemokine receptor mutant CX3CR1-M280 has impaired adhesive function and correlates with protection from cardiovascular disease in man. Journal of Clinical Investigation 111(8):1241-50 (2003).


Story Source:

The above story is based on materials provided by NIH/National Institute Of Allergy And Infectious Diseases. Note: Materials may be edited for content and length.


Cite This Page:

NIH/National Institute Of Allergy And Infectious Diseases. "Gene Variation In Immune System Cells Lowers Heart Disease Risk." ScienceDaily. ScienceDaily, 16 April 2003. <www.sciencedaily.com/releases/2003/04/030416085438.htm>.
NIH/National Institute Of Allergy And Infectious Diseases. (2003, April 16). Gene Variation In Immune System Cells Lowers Heart Disease Risk. ScienceDaily. Retrieved October 26, 2014 from www.sciencedaily.com/releases/2003/04/030416085438.htm
NIH/National Institute Of Allergy And Infectious Diseases. "Gene Variation In Immune System Cells Lowers Heart Disease Risk." ScienceDaily. www.sciencedaily.com/releases/2003/04/030416085438.htm (accessed October 26, 2014).

Share This



More Health & Medicine News

Sunday, October 26, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Texas Nurse Nina Pham Cured of Ebola

Texas Nurse Nina Pham Cured of Ebola

AFP (Oct. 25, 2014) — An American nurse who contracted Ebola while caring for a Liberian patient in Texas has been declared free of the virus and will leave the hospital. Duration: 01:01 Video provided by AFP
Powered by NewsLook.com
Toxin-Packed Stem Cells Used To Kill Cancer

Toxin-Packed Stem Cells Used To Kill Cancer

Newsy (Oct. 25, 2014) — A Harvard University Research Team created genetically engineered stem cells that are able to kill cancer cells, while leaving other cells unharmed. Video provided by Newsy
Powered by NewsLook.com
IKEA Desk Converts From Standing to Sitting With One Button

IKEA Desk Converts From Standing to Sitting With One Button

Buzz60 (Oct. 24, 2014) — IKEA is out with a new convertible desk that can convert from a sitting desk to a standing one with just the push of a button. Jen Markham explains. Video provided by Buzz60
Powered by NewsLook.com
Ebola Protective Suits Being Made in China

Ebola Protective Suits Being Made in China

AFP (Oct. 24, 2014) — A factory in China is busy making Ebola protective suits for healthcare workers and others fighting the spread of the virus. Duration: 00:38 Video provided by AFP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
 
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:  

Breaking News:

Strange & Offbeat Stories

 

Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:  

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile iPhone Android Web
Follow Facebook Twitter Google+
Subscribe RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins