The findings point to a genetic explanation for how smoking can lead to the plaque buildup that stiffens arteries and causes heart disease, said the report in the journal Circulation.
"This has been one of the first big steps towards solving the complex puzzle of gene-environment interactions that lead to coronary heart disease," said co-author Danish Saleheen, assistant professor of biostatistics and epidemiology at the Perelman School of Medicine at the University of Pennsylvania.
Researchers pooled genetic data on more than 140,000 people from more than two dozen earlier studies, with a particular focus on regions of the genome that have been previously associated with a higher risk of plaque buildup in the heart's arteries.
"A change in a single DNA 'letter' on chromosome 15, near the gene that expresses an enzyme (ADAMTS7) produced in blood vessels, was associated with a 12 percent reduction in heart risk in nonsmokers," said the report.
"However, smokers with this same variation had only a five percent lower risk of coronary heart disease -- reducing by over half the protective effect of this genetic variation."
Follow-up lab studies showed that in cells that line arteries of the human heart, the production of the enzyme ADAMTS7 dropped significantly when the cells contained this single-letter DNA variant.
