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Transcript
Key Genetic Risk Factor for Heart Disease: Identification of molecular chain of command of coronary heart disease may lay groundwork for genetic therapies Are you at increased risk of coronary heart disease (CHD)? If so, what can you do about it? While lifestyle plays a big role, we know that CHD tends to cluster in families and has a substantial hereditary component. “Up to 50 per cent of an individual’s risk for CHD lies within his/her DNA,” says Heart and Stroke Foundation of Canada/Pfizer Fellow 2010-2011 Dr. Olga Jarinova. “We are trying to understand what role genetics plays in disease progression and hope that this research will eventually enable development of targeted therapeutic approaches.” Dr. Jarinova, a researcher at the University of Ottawa Heart Institute, is following up on groundbreaking research performed at the institute that sheds light on a small region of DNA within chromosome 9. Previously, Dr. Ruth McPherson and colleagues identified 9p21 risk allele, a DNA variant on chromosome 9 that is the strongest genetic risk for CHD discovered to date. One in four people carry two copies of the risk allele that increases the likelihood of CHD – independent of other known risk factors such as smoking, high blood cholesterol, diabetes or high blood pressure – by one and a half times. Of interest here is ANRIL, a regulator gene known to suppress cell proliferation and control the production of proteins by other genes. Dr. Jarinova and colleagues have previously reported differences in the activities and function of ANRIL in individuals with two risk alleles. As she explains, the 9p21 risk allele alters the activity of ANRIL, reducing the production of these proteins. Lower protein levels allow increased cell growth and reproduction, including the cells involved in arterial plaque formation. Now, Dr. Jarinova is trying to find out how exact DNA changes within this region increase individual risk for CHD. “We strive to understand the role of 9p21 in the molecular chain of command that increases the risk of heart disease,” Dr. Jarinova says. Given the significance of hereditary factors in CHD, studying the effects of the risk allele has significant implications for comprehensive prevention and treatment strategies for people who inherited it from their parents. Dr. Jarinova notes that people with the risk variant have higher levels of ANRIL. “If that’s the case, we can potentially develop therapeutics that will bring levels of ANRIL back to normal,” she says. “There are some things that are within our immediate control, such as diet and exercise but there also others that we were born with and can’t control very easily,” says Dr. Jarinova. “That’s why it is important to learn about our genetic risks − this knowledge can translate into targeted therapeutics that could give us additional protection against heart disease. There’s so much more to learn about risk factors. Right now, exciting opportunities are opening up for us.”