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Genes + Environment = Disease Risk

MedMagSpring10-Genes Environment A UCLA STUDY reveals how human genes interact with their environment to boost disease risk. Published online in 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,” says principal investigator Jake Lusis, Ph.D., a professor of medicine and human genetics and of microbiology, immunology and molecular genetics. “Most research, however, has focused on unraveling the genetic component of disease risk, while ignoring the effect of environmental stimuli.”

The UCLA study examined how the molecular interaction between the two helps lead to disease. “Smoking and high cholesterol, for example, each increases a person’s risk for heart disease,” Dr. Lusis points out. “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 trimmed from donated hearts prior to transplantation, Dr. Lusis and his team cultured cells from the inner lining of blood vessels. To mimic environmental stress, the scientists exposed the cells to fats that incite inflammation and lead to atherosclerosis. Then they compared the normal expression pattern of the cells’ genes to their activity under stress.

“The genes responded differently to inflammation depending on their genetic makeup,” says 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 context,” she adds. “The missing link lies in the intersection of genes with their environment.”


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