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Smoking linked to loss of cardioprotection conferred by ADAMTS7 variant
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The cardioprotective effects of a variant of the ADAMTS7 gene, which decreases levels of an enzyme linked to fatty plaques and CHD, are diminished by smoking, researchers reported 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 [for CHD],” Muredach P. Reilly, MBBCH, MSCE, Herbert and Florence Irving Professor of Medicine and director of the Irving Institute for Clinical and Translational Research at Columbia University Medical Center, said in a press release.
Reilly and colleagues analyzed 60,919 individuals with CHD and 80,243 controls from 29 cohorts to determine interactions between smoking and genes for variants at 45 loci known to be linked to CHD risk.
The researchers identified an interaction at a variant upstream of the ADAMTS7 gene, determining that every T allele of rs7178051 conferred 12% lower risk for CHD in people who never smoked (P = 1.3 x 10-16) but only 5% lower risk for CHD in those who had ever smoked (P = 2.5 x 10-4).
Reilly and colleagues determined that the interaction equated to a 60% loss in protection against CHD conferred by the variant in smokers (P for interaction = 8.7 x 10-5).
The protective T allele conferred reduced expression of ADAMTS7 in aortic endothelial cells and lymphoblastoid cell lines, but exposing coronary artery smooth muscle cells to cigarette smoke extract caused an induction of ADAMTS7, according to the researchers.
“This study is an important example of the emerging field of precision medicine and precision public health,” Reilly said in the release. “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 most efficiently.” – by Erik Swain
Disclosures: Reilly reports no relevant financial disclosures. Another researcher reports receiving support from Eli Lilly, Genentech, Pfizer and Regeneron.
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