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New genetic loci for MI and atherosclerosis found
Recent genome-wide association studies have identified several novel loci associated with coronary artery disease and myocardial infarction, however these represent only a small proportion of the inherited component of these disorders. Furthermore, it is not clear whether these loci contribute to the development of atherosclerosis, or whether they may influence the stability of atherosclerotic plaque. Therefore, this study was designed to investigate whether genetic factors predisposing to MI in patients with coronary atherosclerosis are distinct from those that associate with the presence of coronary atherosclerosis.
The authors used coronary angiography to assess CAD phenotypes, and performed genome-wide association studies on those with coronary artery disease (n=12 393) and those without (n=7383). To specifically identify those loci that predisposed to MI, the authors also compared patients who had angiographic CAD and myocardial infarction (n=5783) with those who had angiographic CAD but had not sustained an MI (n=3644).
A novel locus, ADAMTS7 was identified in the comparison of patients with angiographic CAD versus controls. Furthermore, when comparing patients who had and had not sustained an MI, a novel association was found at the ABO locus, attributable to a glycotransferase-deficient enzyme that encodes the ABO blood group O, previously proposed to protect against MI.
The findings of this genome-wide association study suggest that hereditary factors that predispose to myocardial infarction may differ from those that predispose to myocardial infarction. Future genetic studies must therefore investigate the link between specific loci and the exact phentoypes of atherosclerosis, plaque rupture, and …
Journals scanned American Journal of Medicine; American Journal of Physiology: Heart and Circulatory Physiology; Annals of Emergency Medicine; Annals of Thoracic Surgery; Archives of Internal Medicine; BMJ; Chest; European Journal of Cardiothoracic Surgery; JAMA; Journal of Clinical Investigation; Journal of Diabetes and its Complications; Journal of Immunology; Journal of Thoracic and Cardiovascular Surgery; Lancet; Nature Medicine; New England Journal of Medicine; Pharmacoeconomics; Thorax.
Reviewers Dr Alistair C Lindsay, Dr Hussain Contractor.
Provenance and peer review Not commissioned; not externally peer reviewed.
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