UCLA study reveals how genes interact with their environment to cause disease

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UCLA study reveals how genes interact with their environment to cause disease

http://www.eurekalert.org/pub_releases/2010-02/uoc--usr021710.php

A UCLA study reveals how human genes interact with their environment to boost

disease risk. Published in the Feb. 18 online edition of the American Journal of

Human Genetics, the findings shed light on why the search for specific gene

variants linked to human diseases can only partly explain common disorders.

" We know that genes and environmental factors influence common human diseases

like heart disease, diabetes and cancer, " explained principal investigator Jake

Lusis, professor of medicine, human genetics and microbiology, immunology and

molecular genetics at the Geffen School of Medicine at UCLA. " Most

research, however, has focused on unraveling the genetic component of disease

risk while ignoring the effect of environmental stimuli. Our study examined how

the molecular interaction between the two helps lead to disease. "

" Smoking and high cholesterol, for example, each increase a person's risk for

heart disease, " he said. " But when you add them together, the total risk exceeds

its parts. Their interaction creates a dangerous synergy that causes damage

beyond what the two can cause independently. "

Unlike earlier studies that focused on a single gene, the UCLA team scrutinized

the activity of thousands of human genes both at rest and under stress. In

particular, the scientists zeroed in on gene expression—the process by which a

gene's DNA sequence is converted into cellular proteins.

Using arteries that surgeons had trimmed from 96 donated hearts prior to organ

transplantation, Lusis and his team cultured cells from the inner lining of the

blood vessels. To mimic environmental stress, the scientists exposed the cells

to fats that incite inflammation and lead to atherosclerosis, or hardening of

the arteries. Then they looked at the cells' genes and compared their normal

expression patterns to their activity under stress.

" The genes responded differently to inflammation depending on their genetic

makeup, " said first author Casey Romanoski, a UCLA graduate student in human

genetics. " About 35 percent of the most affected genes were influenced by the

interaction between their genetic variants and the fats. "

" You can't effectively study genes divorced from their environment, " she added.

" The missing link lies in the intersection of genes with their environment. "

" Our findings demonstrate that these interactions are important in humans and

should be considered in genetic research, " said Lusis. " Improving our

understanding of the molecular architecture of disease may one day provide us

with a new tool for how we address common disorders like cancer, diabetes and

heart disease. "

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The National Heart, Lung and Blood Institute and the American Heart Association

funded the research.