Lancet: Some genetic profiles increase CAD risk, others increase MI risk

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Certain genetic profiles increase both risk of coronary artery disease (CAD) and risk of MI in those with CAD, according to two genome-wide association studies published online Jan. 14 in the Lancet.

The authors tested whether genetic factors distinctly contribute to either development of coronary atherosclerosis or, specifically, to MI in existing coronary atherosclerosis.

To identify loci that predispose to angiographic CAD, Muredach P. Reilly, MBBS, from the Cardiovascular Institute at the University of Pennsylvania in Philadelphia, and colleagues compared 12,393 individuals with CAD disorder with 7,383 controls without CAD disorder. To identify loci that predispose to heart attacks, the researchers compared 5,783 patients who had angiographic CAD and had a heart attack with 3,644, who had angiographic CAD but no heart attack.

In the comparison of patients with angiographic CAD versus controls, they identified a novel locus, ADAMTS7. In the comparison of patients with angiographic CAD who had MI versus those with angiographic CAD but no MI, they identified a novel association at the ABO locus.

"Discovery of ABO as the top locus for MI in patients with angiographic CAD is notable, in view of decades of work suggesting a relation between ABO blood-groups and both thrombosis and coronary heart disease,” the authors wrote.

According to Reilly and colleagues, the ABO association was attributable to the glycotransferase-deficient enzyme that encodes the ABO blood group O phenotype previously proposed to protect against MI.

The authors concluded that the relation to specific CAD phenotypes might modify how novel loci are applied in personalized risk assessment and used in the development of novel therapies for CAD.

In the accompanying commentary, Luca A. Lotta, MD, and Flora Peyvandi, MD, PhD, from the Angelo Bianchi Bonomi Hemophilia and Thrombosis Centre, and the University of Milan in Italy, wrote: "As in other genome-wide association studies, biological explanations for the identified associations are still not evident. The field of genetics is rapidly moving forward and large re-sequencing studies, with next-generation platforms, will probably compete with or even replace genome-wide association studies as the gold-standard for the identification of disease-related genes or variants. These studies might also provide insights into associations identified by genome-wide association studies.

“Irrespective of the future, Reilly and colleagues’ idea—to address the phenotypic complexity of these diseases with creative and rigorous study designs—will not be rendered outdated by technological and methodological developments, simply because it does not rely on any specific technique,” Lotta and Peyvandi concluded.

The PennCath and MedStar studies were supported by the University of Pennsylvania, by the MedStar Health Research Institute at Washington Hospital Center in Washington, D.C., and by a research grant from GlaxoSmithKline.