An analysis of two genome-wide association studies has shown that certain genetic profiles increase both risk of coronary artery disease (CAD) and risk of heart attacks (myocardial infarction) in those with CAD. The Article is published Online First and in an upcoming Lancet, and is by Dr Muredach P Reilly, Cardiovascular Institute, University of Pennsylvania , Philadelphia, PA, USA, and colleagues.
To identify loci that predispose to angiographic coronary artery disease (CAD), the authors compared 12,393 individuals with CAD disorder with 7383 controls who did not. To identify loci that predispose to heart attacks, they compared 5783 patients who had angiographic CAD and had a heart attack with 3644 who had angiographic CAD but no heart attack.
The researchers identified a new locus, ADAMTS7, which increased the risk of developing CAD. In the heart-attack comparison, the authors found a new association at the ABO blood group locus. They found that the same gene that codes for the enzyme behind people being blood group O offered protection against heart attacks.
They say: “Discovery of ABO as the top locus for myocardial infarction 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.”
They conclude: “Our findings indicate that specific genetic variants predispose to the development of coronary atherosclerosis whereas others predispose to subsequent plaque rupture and acute heart attack…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 a linked Comment, Dr Luca A Lotta and Dr Flora Peyvandi, Angelo Bianchi Bonomi Hemophilia and Thrombosis Centre, and Luigi Villa Foundation, University of Milan, Italy, say: “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.”
Source: The Lancet