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Review
. 2012 Jan 20;110(2):337-55.
doi: 10.1161/CIRCRESAHA.110.230854.

Genetic basis of atherosclerosis: insights from mice and humans

Ioannis M Stylianou  1 , Robert C Bauer, Muredach P Reilly, Daniel J Rader
Affiliations
Review

Genetic basis of atherosclerosis: insights from mice and humans

Ioannis M Stylianou et al. Circ Res. .

Abstract

Atherosclerosis is a complex and heritable disease involving multiple cell types and the interactions of many different molecular pathways. The genetic and molecular mechanisms of atherosclerosis have, in part, been elucidated by mouse models; at least 100 different genes have been shown to influence atherosclerosis in mice. Importantly, unbiased genome-wide association studies have recently identified a number of novel loci robustly associated with atherosclerotic coronary artery disease. Here, we review the genetic data elucidated from mouse models of atherosclerosis, as well as significant associations for human coronary artery disease. Furthermore, we discuss in greater detail some of these novel human coronary artery disease loci. The combination of mouse and human genetics has the potential to identify and validate novel genes that influence atherosclerosis, some of which may be candidates for new therapeutic approaches.

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Figures

Figure 1
Figure 1. Phenotypic Progression of Atherosclerosis in mouse and humans
[A] Approximate progression of observable atherosclerosis in mouse models, noting that double knockouts (DKOs) on either the Ldlr−/− or Apoe−/− backgrounds can have decrease as well as increased atherosclerosis. [B] An approximate illustration of clinical characterization of atherosclerosis in humans.
Figure 2
Figure 2. The 9p21 human CAD locus and the orthologous mouse region
Horizontal lines indicate the full contiguous length of the labeled transcript. [A] 400,000 bases near the 9p21 CAD locus. The “CAD risk interval” indicates the region containing the most GWSA SNPs for CAD. [B] 400,000 bases surrounding the orthologous mouse region of the CAD locus on human 9p21. A recent update of the mouse genome at this locus (Assembly NCBIM37, Gene build Jan 2011) indicates that there is a region lacking overlapping sequenced contigs (designated “Unknown sequence”) which may be as large as 50,000 bases. The sequenced contigs flanking this region are themselves small and may indicate a region of excessive repetitive DNA preventing the ability to confidently sequence the region.
See this image and copyright information in PMC

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