The Genetic Basis of Peripheral Arterial Disease: Current Knowledge, Challenges, and Future Directions

Iftikhar J. Kullo, Nicholas J. Leeper

Research output: Contribution to journalArticle

34 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1551-1560
Number of pages10
JournalCirculation research
Volume116
Issue number9
DOIs
StatePublished - Apr 24 2015

Keywords

  • epigenomics
  • genome-wide association study
  • molecular epidemiology
  • peripheral arterial disease

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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