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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2000;20:283.)
© 2000 American Heart Association, Inc.

Editorials

IRS-1 Variant

A New Risk Factor for Coronary Artery Disease?

P. Delafontaine, MD, FACC¹

¹ Professor of Medicine and, Chairman, Division of Cardiology, University Hospital, Geneva, Switzerland
From the Division of Cardiology, University Hospital, Geneva, Switzerland.

Correspondence to P. Delafontaine, MD, FACC, Professor of Medicine, Chairman, Division of Cardiology, University Hospital, Rue Micheli-du-Crest 24, 1211 Geneva 14, Switzerland. E-mail Patrice.Delafontaine@hcuge.ch

The genetic predisposition to develop coronary artery disease, while well established,^{1 2 3} is incompletely understood. Much attention has focused on lipoprotein abnormalities that may contribute to this genetic predisposition.^{3 4} Another recent candidate has been a polymorphism of the angiotensin-converting enzyme gene, specifically the DD genotype, that has been associated with higher circulating levels of angiotensin-converting enzyme activity and has been found in some studies, but not all, to be a risk factor for myocardial infarction.^{5 6}

In a recent issue of Arteriosclerosis, Thrombosis, and Vascular Biology (Arterioscler Thromb Vasc Biol. 1999;19:2975–2980), Baroni and coworkers⁷ have studied the frequency of a mutation of the insulin receptor substrate-1 (IRS-1) gene in 318 patients with angiographic evidence of a coronary artery stenosis of >50%. The frequency of this mutation was 2.5-fold higher in these patients compared with 208 control individuals. When adjusted for other risk factors, the relative risk of angiographic coronary disease attributable to the IRS-1 polymorphism was 3-fold, and it increased to 7-fold and 23-fold, respectively, in obese patients and in patients with the insulin resistance syndrome. The latter has been defined as the presence of 2 or more characteristics that include hypertension, obesity, plasma triglycerides >2.26 mmol/L (200 mg/dL), and high fasting insulin levels. Thus, this study provides a new candidate gene potentially contributing to the genetic predisposition to develop coronary artery disease, a polygenic disorder.

The mechanisms whereby the glycine-to-arginine substitution at codon 972 of the IRS-1 gene could lead to an increased risk for coronary disease are not clear. . . . [Full Text of this Article]

This article has been cited by other articles:

				C.-T. Tsai, J.-J. Hwang, L.-P. Lai, F.-T. Chiang, and Y.-Z. Tseng IRS-1 Gly971Arg Variant Is Not a New Risk Factor for Coronary Artery Disease in the Taiwanese Population Arterioscler Thromb Vasc Biol, January 1, 2002; 22(1): 194 - 194. [Full Text] [PDF]