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(Circulation. 2004;110:1868-1873.)
© 2004 American Heart Association, Inc.

Basic Science for Clinicians

Genetic Basis of Atherosclerosis: Part I

New Genes and Pathways

Aldons J. Lusis, PhD; Alan M. Fogelman, MD; Gregg C. Fonarow, MD

From the Division of Cardiology (A.J.L., A.M.F., G.C.F.), the Department of Microbiology, Immunology and Molecular Genetics (A.J.L.), and the Department of Human Genetics (A.J.L.), David Geffen School of Medicine at University of California, Los Angeles.

Correspondence to Aldons J. Lusis, Department of Medicine/Division of Cardiology, 47-123 CHS, Los Angeles, CA 90095-1679. E-mail jlusis@mednet.ucla.edu

Key Words: atherosclerosis • diabetes mellitus • genetics • lipoproteins • mapping

An extract of the first 250 words of the full text is provided, because this article has no abstract.

Atherosclerosis, the primary cause of coronary heart disease (CHD), involves numerous cell types and organs and a number of disparate physiological processes (see Figure 1).^1–3 It is not surprising, then, that the genetic basis of CHD is complex. This complexity is clearly illustrated by studies of rodent models; for example, experiments with transgenic and gene-targeted mice have revealed >100 genes that can influence the development of atherosclerotic lesions. The purpose of this review is to provide a brief overview of our current understanding of the genetic factors that contribute to susceptibility to atherosclerosis in human populations (Part I) and then to examine the clinical implications of this knowledge (Part II).

View larger version (90K): [in this window] [in a new window]   Figure 1. Candidate genes for genetic susceptibility to CHD and some pathways thought to be involved in development and rupture of atherosclerotic lesions. A, Early stages of lesion formation; B, later stages. Many genes shown here have been examined in population-association studies, but only a fraction have been convincingly confirmed as playing role in CHD or genetic susceptibility to its risk factors. Genes with preliminary evidence of association with CHD are shown in red. (For detailed discussion of pathways based largely on transgenic studies in mice, see references 1 through 3.) 5-HT2A receptor indicates serotonin 2A receptor; ACE, angiotensin-converting enzyme; ADD1, adducin 1; AGE, advanced glycosylation end product; aP2, fatty acid–binding protein; BMPs, bone morphogen proteins; C3, complement component 3; CCR2, chemokine receptor 2; CLPN10, calpain 10; COX2, cyclooxygenase-2; CRP, C-reactive protein; CYP7A, cholesterol 7-reductase; EL, endothelial lipase; . . . [Full Text of this Article]

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