The pathophysiological role of novel pulmonary arterial hypertension gene SOX17.
Yukyee WuJohn WhartonRachel WaltersEleni VasilakiJurjan AmanLan ZhaoMartin R WilkinsChristopher J RhodesPublished in: The European respiratory journal (2021)
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.
Keyphrases
- pulmonary arterial hypertension
- transcription factor
- pulmonary hypertension
- copy number
- genome wide identification
- pulmonary artery
- polycyclic aromatic hydrocarbons
- mitochondrial dna
- stem cells
- genome wide
- dna binding
- poor prognosis
- multiple sclerosis
- heart failure
- emergency department
- gene expression
- cancer therapy
- coronary artery
- left ventricular
- mitral valve
- drug delivery
- long non coding rna
- african american
- genome wide analysis