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20-01-2011 | Cardiology | Article

MI risk gene locus distinct from CAD locus found

Abstract

Free abstract

MedWire News: Results of two genome-wide association studies (GWAS) suggest that an association exists between the ADAMTS7 gene locus and the development of coronary artery disease (CAD).

The findings also show an association between the ABO gene locus and a predisposition to future myocardial infarction (MI) in patients with CAD.

"Our results indicate that specific genetic variants predispose to the development of coronary atherosclerosis whereas others predispose to subsequent plaque rupture and acute MI," explain the authors in The Lancet.

In the first GWAS, 12,393 angiographically-diagnosed CAD patients and 7383 CAD-free controls were examined to identify genetic loci associated with CAD.

The researchers report that the risk (C) allele of the single-nucleotide polymorphism (SNP) rs1994016, at the locus containing the ADAMTS7 metalloproteinase gene, was associated with a 19% increased risk for CAD.

Furthermore, genes immediately up- or downstream of the ADAMTS7 gene showed weak linkage disequilibrium, which Muredach Reilly (University of Pennsylvania Medical Center, Philadelphia, USA) and team say supports the belief that ADAMTS7 is the CAD-associated gene at the identified locus.

The second study, involving 5783 CAD patients with MI and 3644 CAD patients without MI, revealed a significant association between 11 SNPs at the ABO gene locus and MI occurrence in CAD patients. Specifically, patients with the risk allele at the most significant SNP (rs514659) had a 21% increased risk for MI development compared with those without the alternative allele.

"The ABO association was attributable to the glycotransferase-deficient enzyme that encodes the ABO blood group O phenotype previously proposed to protect against MI," say Reilly and co-authors.

In an accompanying commentary, Luca Lotta (University of Milan, Italy) and Flora Peyvandi (Baylor College of Medicine, Texas, Houston, USA) highlighted that despite that encouraging study findings, "biological explanations for the identified associations are still not evident."

Reilly and team conclude: "Translation of GWAS discoveries for CAD into prognostic and therapeutic benefit will need greater insights into the relation between each locus and the phenotype of atherosclerosis, plaque rupture, and thrombosis."

MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a trading division of Springer Healthcare Limited. © Springer Healthcare Ltd; 2011

By Lauretta Ihonor

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