Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

First link found in humans between common gene and artery-clogging disease

31.12.2003


Study in NEJM indicates dietary fatty acids may influence atherosclerosis in a segment of the population genetically at risk



Scientists have found the first strong link in humans between a common gene and risk for the disease that leads to most heart attacks and strokes, according to results of a study by researchers at the Keck School of Medicine of the University of Southern California and the David Geffen School of Medicine at UCLA.

People with a variant form of a gene called 5-lipoxygenase (ALOX5) have a greater risk of atherosclerosis, a build-up of cholesterol in artery walls that contributes to heart disease, scientists report in the Jan. 1 issue of the New England Journal of Medicine. The high-risk form of ALOX5 occurred in about 5 percent of participants in the Los Angeles Atherosclerosis Study, which follows the cardiovascular health of 470 utility workers in Southern California.


Researchers have known for many years that atherosclerosis risk may run in families, yet the genetic markers known to increase risk for atherosclerosis either were rare or made only a slight difference. This new finding, however, indicates that a substantial proportion of people carry a form of ALOX5 that may wield potent effects on cardiovascular disease.

"One of the most interesting aspects of this new finding is that the effect of the ALOX5 gene on atherosclerosis depends upon diet," says co-author James Dwyer, Ph.D., professor of preventive medicine at the Keck School of Medicine of USC and the Los Angeles Atherosclerosis Study’s principal investigator. "The adverse effect of this gene is increased by dietary intake of certain n-6 polyunsaturated fats, while the adverse effect is blocked by intake of fish oils containing n-3 polyunsaturated fatty acids."

For those who carry a high-risk form of ALOX5, the "bad" fats are two n-6 polyunsaturated fats called arachidonic acid and linoleic acid. Arachidonic acid is found in some meats, while linoleic acid is found in many vegetable oils. The "good" fats for this group are n-3 (or omega-3) fatty acids, found mainly in oily fish such as salmon.

This diet-gene interaction makes scientific sense, since the ALOX5 protein serves to convert fatty acids into molecules involved in inflammation, and scientists believe atherosclerosis is an inflammatory process.

Results also suggest that people with a high-risk form of ALOX5 could reduce their risk by eating less n-6 polyunsaturated fats and more n-3 polyunsaturated fatty acids. In the rest of the population, eating these fatty acids seems to have little impact on atherosclerosis, Dwyer adds-although there is substantial evidence that consuming a lot of n-3 fatty acids from fish oils prevents arrhythmias involved in sudden cardiac death.

Co-author Hooman Allayee, Ph.D., human genetics researcher at the David Geffen School of Medicine at UCLA, noted that earlier research links ALOX5 to asthma, so physicians might potentially prescribe existing asthma medications to prevent and control atherosclerosis in those genetically at high risk.

"Our conclusions suggest that 5-lipoxygenase could be used as a genetic marker for heart disease, and should lead to improved diagnosis, prevention and treatment for atherosclerosis," Allayee says.

The team’s work was driven by a mouse model developed by Margarete Mehrabian, Ph.D., senior author and UCLA assistant professor of human genetics. She was the first to show that eliminating the gene from the mouse genome helps protect against atherosclerosis, even when the rodent ate a fat-heavy diet. Other researchers have shown that knocking out other inflammatory genes can protect mice against atherosclerosis, but attempts to link alterations in inflammatory genes to atherosclerotic disease in humans generally has been disappointing.

For this study, the team examined 470 healthy middle-aged women and men. Researchers recorded each participant’s diet over 18 months and used ultrasound to measure the thickness of carotid artery walls in each participant-a gauge of atherosclerosis and heart disease risk.

Scientists also examined the ALOX5 gene in DNA sampled from each participant. The ALOX5 gene can be found in a few different varieties, or polymorphisms, within the population, in addition to the common form of the gene.

The scientists found that artery walls were as much as 18 percent thicker among participants who did not have the common form of ALOX5. And walls thickened faster among those with a high-risk version of ALOX5 who ate more food containing n-6 polyunsaturated fatty acids, while a diet abundant in n-3 polyunsaturated fatty acids seemed to protect them.

Researchers found the ALOX5 variations more frequently in certain ethnic groups. About 20 percent of African Americans and Asian Americans had the genetic variant, compared to less than 5 percent of Latinos and non-Latino whites.


A grant from the National Institutes of Health supports the Los Angeles Atherosclerosis Study. The American Heart Association also sponsored the research.

James H. Dwyer, Hooman Allayee, Kathleen M. Dwyer, Jing Fan, Huiyun Wu, Rebecca Mar, Aldons J. Lusis, Margarete Mehrabian, "Arachidonate 5-lipoxygenase promoter genotype, dietary arachidonic acid, and atherosclerosis. The Los Angeles Atherosclerosis Study," New England Journal of Medicine. 2004, Vol.350, No. 1, pp. 29-37.

Jon Weiner | EurekAlert!
Further information:
http://www.usc.edu/

More articles from Studies and Analyses:

nachricht Drone vs. truck deliveries: Which create less carbon pollution?
31.05.2017 | University of Washington

nachricht New study: How does Europe become a leading player for software and IT services?
03.04.2017 | Fraunhofer-Institut für System- und Innovationsforschung (ISI)

All articles from Studies and Analyses >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Can we see monkeys from space? Emerging technologies to map biodiversity

An international team of scientists has proposed a new multi-disciplinary approach in which an array of new technologies will allow us to map biodiversity and the risks that wildlife is facing at the scale of whole landscapes. The findings are published in Nature Ecology and Evolution. This international research is led by the Kunming Institute of Zoology from China, University of East Anglia, University of Leicester and the Leibniz Institute for Zoo and Wildlife Research.

Using a combination of satellite and ground data, the team proposes that it is now possible to map biodiversity with an accuracy that has not been previously...

Im Focus: Climate satellite: Tracking methane with robust laser technology

Heatwaves in the Arctic, longer periods of vegetation in Europe, severe floods in West Africa – starting in 2021, scientists want to explore the emissions of the greenhouse gas methane with the German-French satellite MERLIN. This is made possible by a new robust laser system of the Fraunhofer Institute for Laser Technology ILT in Aachen, which achieves unprecedented measurement accuracy.

Methane is primarily the result of the decomposition of organic matter. The gas has a 25 times greater warming potential than carbon dioxide, but is not as...

Im Focus: How protons move through a fuel cell

Hydrogen is regarded as the energy source of the future: It is produced with solar power and can be used to generate heat and electricity in fuel cells. Empa researchers have now succeeded in decoding the movement of hydrogen ions in crystals – a key step towards more efficient energy conversion in the hydrogen industry of tomorrow.

As charge carriers, electrons and ions play the leading role in electrochemical energy storage devices and converters such as batteries and fuel cells. Proton...

Im Focus: A unique data centre for cosmological simulations

Scientists from the Excellence Cluster Universe at the Ludwig-Maximilians-Universität Munich have establised "Cosmowebportal", a unique data centre for cosmological simulations located at the Leibniz Supercomputing Centre (LRZ) of the Bavarian Academy of Sciences. The complete results of a series of large hydrodynamical cosmological simulations are available, with data volumes typically exceeding several hundred terabytes. Scientists worldwide can interactively explore these complex simulations via a web interface and directly access the results.

With current telescopes, scientists can observe our Universe’s galaxies and galaxy clusters and their distribution along an invisible cosmic web. From the...

Im Focus: Scientists develop molecular thermometer for contactless measurement using infrared light

Temperature measurements possible even on the smallest scale / Molecular ruby for use in material sciences, biology, and medicine

Chemists at Johannes Gutenberg University Mainz (JGU) in cooperation with researchers of the German Federal Institute for Materials Research and Testing (BAM)...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Plants are networkers

19.06.2017 | Event News

Digital Survival Training for Executives

13.06.2017 | Event News

Global Learning Council Summit 2017

13.06.2017 | Event News

 
Latest News

Study shines light on brain cells that coordinate movement

26.06.2017 | Life Sciences

Smooth propagation of spin waves using gold

26.06.2017 | Physics and Astronomy

Switchable DNA mini-machines store information

26.06.2017 | Information Technology

VideoLinks
B2B-VideoLinks
More VideoLinks >>>