Download Key Genetic Risk Factor for Heart Disease:

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.”