Scientists at Children's Hospital Oakland Research Institute (CHORI), the University of Iowa and Roche Molecular Systems are the first to identify a new gene variant that makes women more susceptible to developing heart disease. The affected gene is called Leukotriene C4 Synthase (LTC4S) and its variant could be identified through a genetic test at birth. The use of such a test would allow physicians to initiate preventative treatments to reduce or even eliminate the risk of heart disease in those women possessing the variant gene.
The study will be published in the February issue of the American Heart Association journal Arteriosclerosis, Thrombosis, and Vascular Biology and was conducted by CHORI Scientists David Iovannisci, Ph.D. and Edward Lammer, M.D.* The study began in 1971 with 11,377 children in Muscatine, Iowa. During the study, researchers periodically evaluated the participants' risks of developing heart disease starting in their teens and into their 40's. Their weight, height, blood pressure, cholesterol and other health factors and risks were recorded between 1971 and 1996. The women and men in the study were selected because they live in the City of Muscatine, Iowa where residents rarely move, which is an ideal component to conduct a multi-year study.
The identification and monitoring of study participants was lead by Ronald Lauer, M.D., from the University of Iowa. Scientists at CHORI were responsible for genotyping DNA samples and drawing the study's conclusions. They hypothesized that inflammation was an important predictor for the development of heart disease. Inflammation is necessary to repair and heal nicks to the lining of blood vessels, which occur daily. The variant form of the LTC4S gene however, leads to an excessive inflammatory response at the site of blood vessel injury. As a result, people who inherit this gene variant don't repair damage to their blood vessels as well as others. Until now, the LTC4S gene variant was only known to cause asthma.
"This is the first direct evidence that a gene known to be linked to asthma is also tied to adult heart disease," said Edward Lammer, M.D., Geneticist at Children's Hospital Oakland Research Institute. "Our work is significant because we made allowances for other risk factors such as smoking, cholesterol and blood pressure levels. Consequently, we believe that the risk is genetic and not significantly influenced by a person's environment," said Dr. Lammer.
Based upon their theory, researchers focused on two key measurements in the study. The first measurement was to identify study participants who had the LTC4S gene variant. Both women and men participated in the study, but the LTC4S gene variant was only linked to early signs of coronary artery disease in women. The second test was to assess two early measurements of coronary artery disease and stroke: 1) calcium build-up within coronary arteries commonly seen in heart attack victims and 2) the thickening of the carotid artery associated with stroke victims. The test results confirmed that those women with the LTC4S gene variant were also at the beginning stages of heart disease. It is important to note that none of the participants in the study have yet been diagnosed with heart disease.
"This is one of the first studies to track the development of heart disease in young people and not the aftermath of the disease in older populations," said David Iovannisci, Ph.D., Assistant Staff Scientist at Children's Hospital Oakland Research Institute. "Our research provides critical clues to help us identify people who are susceptible to heart disease long before the disease presents itself and when treatments may be most effective."
These research results add to growing evidence suggesting that inflammatory responses are very important for development of coronary artery disease and stroke. Consequently, researchers believe their findings could assist in the development of personalized medicine for people with this altered inflammatory response. New drugs that target inflammatory responses may prove to be effective for preventing adult heart disease and stroke.
*Researchers from the University of Iowa include: Larry T. Mahoney, Patricia H. Davis, Ronald M. Lauer and Trudy L. Burns. Researchers from Roche Molecular Systems include: Lori Steiner and Suzanne Cheng.
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