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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2007;27:2068.)
© 2007 American Heart Association, Inc.

Brief Reviews

Genetic Susceptibility to Peripheral Arterial Disease: A Dark Corner in Vascular Biology

Joshua W. Knowles; Themistocles L. Assimes; Jun Li; Thomas Quertermous; John P. Cooke

From the Division of Cardiovascular Medicine (J.W.K., T.L.A., T.Q., J.P.C.), Stanford University School of Medicine, Stanford, Calif; Stanford Human Genome Center, Department of Genetics (J.L.), Stanford University School of Medicine, Palo Alto, Calif.

Correspondence to Joshua W. Knowles, Falk Cardiovascular Research Building, Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA, 94305-5406. E-mail knowelj{at}stanford.edu

Peripheral arterial disease (PAD) is characterized by reduced blood flow to the limbs, usually as a consequence of atherosclerosis, and affects 12 million Americans. It is a common cause of cardiovascular morbidity and an independent predictor of cardiovascular mortality. Similar to other atherosclerotic diseases, such as coronary artery disease, PAD is the result of the complex interplay between injurious environmental stimuli and genetic predisposing factors of the host. Genetic susceptibility to PAD is likely contributed by sequence variants in multiple genes, each with modest effects. Although many of these variants probably alter susceptibility both to PAD and to coronary artery disease, it is likely that there exists a set of variants specifically to alter susceptibility to PAD. Despite the prevalence of PAD and its high societal burden, relatively little is known about such genetic variants. This review summarizes our limited present knowledge and gives an overview of recent, more powerful approaches to elucidating the genetic basis of PAD. We discuss the advantages and limitations of genetic studies and highlight the need for collaborative networks of PAD investigators for shedding light on this dark corner of vascular biology.

Key Words: peripheral vascular disease • genetics • epidemiology • atherosclerosis

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