title: Epigenomic changes associated with impaired norepinephrine transporter function in postural tachycardia syndrome.
abstract: The postural tachycardia syndrome (POTS) is characterised clinically by symptoms of light-headedness, palpitations, fatigue and exercise intolerance occurring with standing and relieved by lying down. Symptoms occur in association with an inappropriate rise in heart rate in the absence of a fall in blood pressure with the assumption of standing. The pathophysiology of POTS is complicated and poorly understood. Plasma norepinephrine (NE) is often elevated in patients with POTS, resulting in consideration of dysfunction of the norepinephrine transporter (NET) encoded by SLC6A2 gene. Whilst some studies have implicated a defect in the SLC6A2 gene, the cause of reduced SLC6A2 expression and function remains unclear. The search to explain the molecular mechanism of NET dysfunction has focused on genetic variation in the SLC6A2 gene and remains inconclusive. More recent studies show epigenetic mechanisms implicated in the regulation of SLC6A2 expression. In this article, we discuss the epigenetic mechanisms involved in SLC6A2 repression and highlight the potential therapeutic application of targeting these mechanisms in POTS.
authors.affiliation: Baker IDI Heart and Diabetes Institute, The Alfred Medical Research and Education Precinct, Melbourne, Victoria 3004, Australia; Department of Pathology, The University of Melbourne, Parkville, Victoria, Australia. Electronic address: abdulwaheed.khan@bakeridi.edu.au.
authors.forename: Abdul Waheed
authors.initials: AW
authors.lastname: Khan
authors.affiliation: Baker IDI Heart and Diabetes Institute, The Alfred Medical Research and Education Precinct, Melbourne, Victoria 3004, Australia. Electronic address: Susan.Corcoran@bakeridi.edu.au.
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Corcoran
authors.affiliation: Baker IDI Heart and Diabetes Institute, The Alfred Medical Research and Education Precinct, Melbourne, Victoria 3004, Australia. Electronic address: Murray.Esler@bakeridi.edu.au.
authors.forename: Murray
authors.initials: M
authors.lastname: Esler
authors.affiliation: Baker IDI Heart and Diabetes Institute, The Alfred Medical Research and Education Precinct, Melbourne, Victoria 3004, Australia; Department of Pathology, The University of Melbourne, Parkville, Victoria, Australia; Central Clinical School, Faculty of Medicine, Monash University, Victoria, Australia. Electronic address: assam.el-osta@bakeridi.edu.au.
authors.forename: Assam
authors.initials: A
authors.lastname: El-Osta
mesh_terms: D057890:Epigenomics; D006339:Heart Rate; D006801:Humans; D009638:Norepinephrine; D050484:Norepinephrine Plasma Membrane Transport Proteins; D054972:Postural Orthostatic Tachycardia Syndrome
chemical_list: D050484:Norepinephrine Plasma Membrane Transport Proteins; D009638:Norepinephrine
keywords: Chromatin; Epigenetics; Gene regulation; Histone modifications; MeCP2; Norepinephrine transporter; Postural tachycardia syndrome