A University of California at Los Angles (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,” Jake Lusis, professor of medicine, human genetics and microbiology, immunology and molecular genetics at the David Geffen School of Medicine at UCLA, said in a news release. “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.”
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.
“We are ultimately interested in understanding the inflammatory process called atherosclerosis, which is the thickening of the arteries and leads to heart attack and stroke. To better understand this process we sought to identify the molecular pathways that predispose an individual to respond to pro-inflammatory stimuli,” first author Casey Romanoski, a UCLA graduate student in human genetics told O&P Business News. “We therefore designed a study to measure thousands of cellular responses with and without exposure to pro-inflammatory oxidized phospholipids in a genetically diverse population of individuals.”
Using arteries that surgeons had trimmed from 96 donated hearts prior to organ transplantation, Lusis, Romanoski and the 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. Then they looked at the cells’ genes and compared their normal expression patterns to their activity under stress.
“We focused on gene expression, which is the intermediate step between DNA and proteins which do much of the work in cells, because gene expression patterns that relate to DNA sequences reveal the potential molecules that may be causing disease,” Romanoski, said. “The genes responded differently to inflammation depending on their genetic makeup. About 35% of the most affected genes were influenced by the interaction between their genetic variants and the fats.”
