Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2015 Apr 24;116(9):1551-60.
doi: 10.1161/CIRCRESAHA.116.303518.

The genetic basis of peripheral arterial disease: current knowledge, challenges, and future directions

Iftikhar J Kullo  1 , Nicholas J Leeper  2
Affiliations
Review

The genetic basis of peripheral arterial disease: current knowledge, challenges, and future directions

Iftikhar J Kullo et al. Circ Res. .

Abstract

Several risk factors for atherosclerotic peripheral arterial disease (PAD), such as dyslipidemia, diabetes mellitus, and hypertension, are heritable. However, predisposition to PAD may be influenced by genetic variants acting independently of these risk factors. Identification of such genetic variants will provide insights into underlying pathophysiologic mechanisms and facilitate the development of novel diagnostic and therapeutic approaches. In contrast to coronary heart disease, relatively few genetic variants that influence susceptibility to PAD have been discovered. This may be, in part, because of greater clinical and genetic heterogeneity in PAD. In this review, we (1) provide an update on the current state of knowledge about the genetic basis of PAD, including results of family studies and candidate gene, linkage as well as genome-wide association studies; (2) highlight the challenges in investigating the genetic basis of PAD and possible strategies to overcome these challenges; and (3) discuss the potential of genome sequencing, RNA sequencing, differential gene expression, epigenetic profiling, and systems biology in increasing our understanding of the molecular genetics of PAD.

Keywords: epigenomics; genome-wide association study; molecular epidemiology; peripheral arterial disease.

PubMed Disclaimer

Figures

Fig. 1
Fig. 1
Arterial pathology in atherosclerotic, inflammatory, and non-atherosclerotic non-inflammatory arteriopathies. Atherosclerosis is characterized by plaques with varying amounts of inflammatory cells, lipid deposition, fibrosis, calcification, cellular necrosis, smooth muscle proliferation and necrosis, disruption of internal elastic lamina. Inflammatory arterial diseases are characterized by marked inflammatory cell infiltration and in the case of large vessel vasculitis, by giant cell formation. Features of non-inflammatory non-atherosclerotic arterial disease vary. In fibromuscular dysplasia, the prominent features are excessive fibroblasts, deposition of increased amounts of extra cellular matrix and relative paucity of inflammatory cells.
Fig. 2
Fig. 2
Family history as a risk factor for PAD. Shown are odds ratios when the affected family member is a monozygotic twin, a dizygotic twin or a sibling.25,27
See this image and copyright information in PMC

References

    1. Fowkes FG, Rudan D, Rudan I, Aboyans V, Denenberg JO, McDermott MM, Norman PE, Sampson UK, Williams LJ, Mensah GA, Criqui MH. Comparison of global estimates of prevalence and risk factors for peripheral artery disease in 2000 and 2010: a systematic review and analysis. Lancet. 2013;382:1329–1340. - PubMed
    1. Allison MA, Ho E, Denenberg JO, Langer RD, Newman AB, Fabsitz RR, Criqui MH. Ethnic-specific prevalence of peripheral arterial disease in the United States. Am J Prev Med. 2007;32:328–333. - PubMed
    1. Selvin E, Erlinger TP. Prevalence of and risk factors for peripheral arterial disease in the United States: results from the National Health and Nutrition Examination Survey, 1999-2000. Circulation. 2004;110:738–-743. - PubMed
    1. Golomb BA, Dang TT, Criqui MH. Peripheral arterial disease: morbidity and mortality implications. Circulation. 2006;114:688–699. - PubMed
    1. Mahoney EM, Wang K, Cohen DJ, Hirsch AT, Alberts MJ, Eagle K, Mosse F, Jackson JD, Steg PG, Bhatt DL. One-year costs in patients with a history of or at risk for atherothrombosis in the United States. Circ Cardiovasc Qual Outcomes. 2008;1:38–45. - PubMed

Publication types

MeSH terms