Scientists Identify 4 Genes Responsible For Levels Of ‘Bad’ Cholesterol
May 16, 2013

Scientists Identify 4 Genes Responsible For Levels Of ‘Bad’ Cholesterol

April Flowers for — Your Universe Online

Texas Biomedical Research Institute scientists have identified four genes in baboons that influence levels of “bad cholesterol,” which could lead to the development of new drug therapies to reduce the risk of heart disease. The findings will be published in the Journal of Lipid Research.

"Our findings are important because they provide new targets for the development of novel drugs to reduce heart disease risk in humans," said Laura Cox, Ph.D., a Texas Biomed geneticist. "Since these genes have previously been associated with cancer, our findings suggest that genetic causes of heart disease may overlap with causes of some types of cancer."

The research team screened a colony of 1,500 baboons to find three half-siblings with low levels of low density lipoprotein (LDL), otherwise known as “bad” cholesterol. They also identified three half-siblings with high levels of LDL. All six animals were fed a high-fat, high-cholesterol diet for seven weeks.

Gene array technology and high throughput sequencers were used to home in on the genes expressed in the two groups. The researchers then differentiated those of the low LDL group from those in the high LDL group, discovering that four genes influence LDL levels. These four genes -- TENC1, ERBB3, ACVR1B, and DGKA -- are part of a signaling pathway that is important for cell survival. Research has shown that disruption of this pathway promotes certain types of cancer.

Scientists have known for a long time that a high level of LDL is a major risk factor for heart disease. Heart disease remains the leading cause of death globally, despite 25 years of concentrated efforts to manage cholesterol levels through changes in lifestyle and drug treatments. According to the American Heart Association, heart disease will account for one out of four US deaths in 2013.

Researchers believe that heart disease results from interactions between genetic and environmental factors, which occur primarily through diet. The contributions of diet are fairly well understood. What needs more understanding, however, is why humans have different LDL levels causing variations in risk for heart disease. To this end, the genetic factors underlying these differences need to be studied.

Such studies are hard to do with people, however, because it is nearly impossible to control what people eat. This is why the Texas Biomed team turned to baboons in order to identify genetic influences to heart disease risk. Baboons are similar to humans in physiology and genetics.

The study´s findings suggest that knowing many of the genes responsible might be necessary to devise effective treatments, as several genes may need to be targeted simultaneously to control the patient´s risk.

The team says the next step is to find the mechanism these genes use to influence LDL. "That starts to give us the specific targets for new therapies." Cox said. She expects this information to be available within two years.