Researchers ID enzyme related to smoking, heart disease

Smoking is known to increase the risk of heart disease, but certain patients carrying a particular gene may be at an even higher risk, according to a new study from Columbia University in New York.

A gene type that reduces levels of the enzyme ADAMTS7, which is associated with artery-clogging fatty plaques and coronary heart disease (CHD), can be counteracted by smoking, diminishing its protective qualities, the research shows. The full study was published May 1 in Circulation.

"Our findings suggest that interventions to inhibit this enzyme would be particularly beneficial for smokers, and they may also prove useful for anyone at heightened risk of coronary heart disease," said Muredach P. Reilly, the lead author on the study, a professor of medicine and director of the Irving Institute for Clinical and Translational Research at Columbia University Medical Center (CUMC), in a statement.

In the study, researchers collected genetic data on more than 140,000 people from 29 other studies and examined 45 small regions of the genome that has previously been linked to a heightened risk of CHD. Reilly and his team had hypothesized that the associated heart risk would be different in smokers.

When they tested the theory, their hypothesis was shown to be valid. When the researchers placed a liquid extract of cigarette smoke to coronary artery cells, their production of enzyme ADAMTS7 more than doubled, showing that smoking could counteract the genetic protection the enzyme provides.

Results showed that by changing a single DNA “letter” in chromosome 15, near the gene that expresses enzyme ADAMTS7, there was a 12 percent reduction in heart risk non-smokers. But smokers with the same variation were shown to only have a 5 percent lower risk of CHD.

"This has been one of the first big steps towards solving the complex puzzle of gene-environment interactions that lead to CHD," said Danish Saleheen, PhD, an author on the study and an assistant professor of biostatistics and epidemiology at the Perelman School of Medicine at the University of Pennsylvania, in a statement.

In future studies, Reilly said he wants to explore the intricate relationships between the enzyme, smoking and CHD, with an emphasis on how those relationships could slow the progression of atherosclerosis.

"This study is an important example of the emerging field of precision medicine and precision public health," Reilly said. "Through these large-scale genetic studies, we're beginning to understand the genetic variations that drive risk in response to certain environmental exposures or lifestyle behaviors. Not everyone reacts the same to the same exposures or behaviors. For example, some people who don't exercise develop diabetes while others do not. So, instead of saying there are rules for everybody, we can specify which interventions will be especially beneficial for specific populations or individuals and focus our health resources more efficiently."