کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5043623 1370587 2017 14 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Epigenomic changes associated with impaired norepinephrine transporter function in postural tachycardia syndrome
ترجمه فارسی عنوان
تغییرات اپی ژنومیک در ارتباط با اختلال عملکرد حمل کننده نوراپی نفرین در سندرم تاکیکاردی موضعی
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب رفتاری
چکیده انگلیسی


- NET dysfunction is evident in disorders like POTS, hypertension, major depression and panic disorder.
- Genetic mutation in SLC6A2 is identified in one familial study.
- Recent evidences suggest that epigenetic mechanisms are involved in deregulation of SLC6A2 expression.
- MeCP2 binding and histone modification at SLC6A2 promoter are associated with reduced SLC6A2 expression in POTS.

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.

In this review, we discuss the currently proposed epigenomic changes in SLC6A2 gene in POTS. Modification of SLC6A2 chromatin is associated with inactive gene transcription and reduced NET dependent NE re uptake, causing increased heart rate in POTS patients.181

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neuroscience & Biobehavioral Reviews - Volume 74, Part B, March 2017, Pages 342-355
نویسندگان
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