麻豆传媒

Some genetic profiles appear to raise the risk of coronary artery disease -- while others specifically boost the risk of heart attack among CAD patients, according to two large genome-wide association studies.

One study found that a newly found locus, ADAMTS7, was associated with an increased risk of atherosclerosis, while a second study found that the ABO locus that encodes for blood type raised the risk of myocardial infarction in patients with heart disease, Muredach Reilly, MD, of the University of Pennsylvania in Philadelphia, and colleagues reported.

"Our results indicate that specific genetic variants predispose to the development of coronary atherosclerosis, whereas others predispose to subsequent plaque rupture and acute myocardial infarction," Reilly and co-authors wrote online in The Lancet.

While recent genome-wide association studies have identified several novel loci for heart disease, only a small proportion of these inherited loci have been identified, the researchers said.

So to see whether genetic factors may contribute to the development of coronary atherosclerosis or MI, Reilly and colleagues looked at data from two genetic association studies that involved coronary angiographic phenotyping -- PennCath and MedStar.

In one study, they compared 12,393 patients who had angiography-proven atherosclerosis with 7,383 disease-free controls. In another, they compared 5,783 patients with coronary artery disease who'd also had a heart attack with another 3,644 patients who had heart disease but no myocardial infarction.

In the first group, the researchers found that a single nucleotide polymorphism (SNP) in ADAMTS7 called rs1994016 exceeded genome-wide significance for coronary artery disease, showing a 14% increased risk of heart disease (P=0.0174).

The variant maps within intron 8 of ADAMTS7, a member of the family of disintegrin and metalloproteinase with thrombospondin motifs proteins, the researchers explained. It is also implicated in the proliferative response to vascular injury, "a process that has parallels to the progressive phase of atherosclerosis," Reilly and co-authors wrote.

In the second population that included heart attack patients, the researchers found that none of the published SNPs for myocardial infarction were significant for heart attack in patients with coronary artery disease.

However, there were 49 other SNPs associated with heart attack in atherosclerosis patients, and the top 11 mapped to one region within ABO, the blood group locus.

Thus, the researchers said, the ABO locus appears to be associated with both atherosclerosis and heart attack but not atherosclerosis alone.

They also saw that in CAD patients, blood group genotypes A, B, and AB had greater odds of having a heart attack than did blood group O.

"The result suggests that ABO blood group O is protective against myocardial infarction in patients with angiographic CAD but is not related to coronary atherosclerosis," they wrote.

The researchers explained that the ABO locus association was likely attributable to the glycotransferase-deficient enzyme that encodes the ABO blood group O phenotype, which has been previously proposed to protect against heart attack.

Although the current report was limited because it included multiple studies -- which could allow for selection bias and confounding -- the researchers said the findings could assist in personalized risk assessment and in development of novel therapies for coronary atherosclerosis.

In an accompanying commentary, Luca Lotta, MD, and Flora Peyvandi, MD, of the Baylor College of Medicine in Houston, Texas, wrote that the biological explanations for the identified associations are still not completely clear, but advances in genetics may provide further insights into these associations.

Still, the editorialists said the researchers' 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."