TY - JOUR
T1 - The Genetic Basis of Peripheral Arterial Disease
T2 - Current Knowledge, Challenges, and Future Directions
AU - Kullo, Iftikhar J.
AU - Leeper, Nicholas J.
N1 - Publisher Copyright:
© 2015 American Heart Association, Inc.
PY - 2015/4/24
Y1 - 2015/4/24
N2 - 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.
AB - 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.
KW - epigenomics
KW - genome-wide association study
KW - molecular epidemiology
KW - peripheral arterial disease
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U2 - 10.1161/CIRCRESAHA.116.303518
DO - 10.1161/CIRCRESAHA.116.303518
M3 - Article
C2 - 25908728
AN - SCOPUS:84942890179
SN - 0009-7330
VL - 116
SP - 1551
EP - 1560
JO - Circulation research
JF - Circulation research
IS - 9
ER -