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UCLA study reveals how genes interact with their environment to cause disease
Date:2/18/2010

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 David 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 expressionthe 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
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Contact: Elaine Schmidt
eschmidt@mednet.ucla.edu
310-794-2272
University of California - Los Angeles
Source:Eurekalert

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