TY - JOUR
T1 - The pathophysiological role of novel pulmonary arterial hypertension gene SOX17
AU - Wu, Yukyee
AU - Wharton, John
AU - Walters, Rachel
AU - Vasilaki, Eleni
AU - Aman, Jurjan
AU - Zhao, Lan
AU - Wilkins, Martin R.
AU - Rhodes, Christopher J.
N1 - Funding Information: Support statement: This work was supported by the Academy of Medical Sciences (grant SBF004\1095) and the British Heart Foundation (grants FS-15-59-31839 and PG/19/17/34275). Funding information for this article has been deposited with the Crossref Funder Registry. Publisher Copyright: Copyright © The authors 2021. For reproduction rights and permissions contact permissions@ersnet.org
PY - 2021/9/1
Y1 - 2021/9/1
N2 - Pulmonary arterial hypertension (PAH) is a progressive disease predominantly targeting pre-capillary blood vessels. Adverse structural remodelling and increased pulmonary vascular resistance result in cardiac hypertrophy and ultimately failure of the right ventricle. Recent whole-genome and whole-exome sequencing studies have identified SOX17 as a novel risk gene in PAH, with a dominant mode of inheritance and incomplete penetrance. Rare deleterious variants in the gene and more common variants in upstream enhancer sites have both been associated with the disease, and a deficiency of SOX17 expression may predispose to PAH. This review aims to consolidate the evidence linking genetic variants in SOX17 to PAH, and explores the numerous targets and effects of the transcription factor, focusing on the pulmonary vasculature and the pathobiology of PAH.
AB - Pulmonary arterial hypertension (PAH) is a progressive disease predominantly targeting pre-capillary blood vessels. Adverse structural remodelling and increased pulmonary vascular resistance result in cardiac hypertrophy and ultimately failure of the right ventricle. Recent whole-genome and whole-exome sequencing studies have identified SOX17 as a novel risk gene in PAH, with a dominant mode of inheritance and incomplete penetrance. Rare deleterious variants in the gene and more common variants in upstream enhancer sites have both been associated with the disease, and a deficiency of SOX17 expression may predispose to PAH. This review aims to consolidate the evidence linking genetic variants in SOX17 to PAH, and explores the numerous targets and effects of the transcription factor, focusing on the pulmonary vasculature and the pathobiology of PAH.
UR - http://www.scopus.com/inward/record.url?scp=85116820068&partnerID=8YFLogxK
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UR - https://www.ncbi.nlm.nih.gov/pubmed/33632800
U2 - https://doi.org/10.1183/13993003.04172-2020
DO - https://doi.org/10.1183/13993003.04172-2020
M3 - Review article
C2 - 33632800
SN - 0903-1936
VL - 58
JO - European respiratory journal
JF - European respiratory journal
IS - 3
M1 - 2004172
ER -