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 AI study of risk factors in type 1 diabetes
06.03.2019 | University of Gothenburg

nachricht Rising CO2 has unforeseen strong impact on Arctic plant productivity
21.02.2019 | Max-Planck-Institut für Meteorologie

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: Revealing the secret of the vacuum for the first time

New research group at the University of Jena combines theory and experiment to demonstrate for the first time certain physical processes in a quantum vacuum

For most people, a vacuum is an empty space. Quantum physics, on the other hand, assumes that even in this lowest-energy state, particles and antiparticles...

Im Focus: Sussex scientists one step closer to a clock that could replace GPS and Galileo

Physicists in the EPic Lab at University of Sussex make crucial development in global race to develop a portable atomic clock

Scientists in the Emergent Photonics Lab (EPic Lab) at the University of Sussex have made a breakthrough to a crucial element of an atomic clock - devices...

Im Focus: Sensing shakes

A new way to sense earthquakes could help improve early warning systems

Every year earthquakes worldwide claim hundreds or even thousands of lives. Forewarning allows people to head for safety and a matter of seconds could spell...

Im Focus: A thermo-sensor for magnetic bits

New concept for energy-efficient data processing technology

Scientists of the Department of Physics at the University of Hamburg, Germany, detected the magnetic states of atoms on a surface using only heat. The...

Im Focus: The moiré patterns of three layers change the electronic properties of graphene

Combining an atomically thin graphene and a boron nitride layer at a slightly rotated angle changes their electrical properties. Physicists at the University of Basel have now shown for the first time the combination with a third layer can result in new material properties also in a three-layer sandwich of carbon and boron nitride. This significantly increases the number of potential synthetic materials, report the researchers in the scientific journal Nano Letters.

Last year, researchers in the US caused a big stir when they showed that rotating two stacked graphene layers by a “magical” angle of 1.1 degrees turns...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

International Modelica Conference with 330 visitors from 21 countries at OTH Regensburg

11.03.2019 | Event News

Selection Completed: 580 Young Scientists from 88 Countries at the Lindau Nobel Laureate Meeting

01.03.2019 | Event News

LightMAT 2019 – 3rd International Conference on Light Materials – Science and Technology

28.02.2019 | Event News

 
Latest News

Researchers measure near-perfect performance in low-cost semiconductors

18.03.2019 | Power and Electrical Engineering

Nanocrystal 'factory' could revolutionize quantum dot manufacturing

18.03.2019 | Materials Sciences

Long-distance quantum information exchange -- success at the nanoscale

18.03.2019 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>