Epigenetic Modification of the Norepinephrine Transporter Gene in Postural Tachycardia Syndrome
Abstract
Objective—: The postural tachycardia syndrome (POTS) has multiple symptoms, chief among which are tachycardia, weakness, and recurrent blackouts while standing. Previous research has implicated dysfunction of the norepinephrine transporter. A coding mutation in the norepinephrine transporter gene ( SLC6A2 ) sequence has been reported in 1 family kindred only. The goal of the present study was to further characterize the role and regulation of the SLC6A2 gene in POTS. Methods and Results—: Sympathetic nervous system responses to head-up tilt were examined by combining norepinephrine plasma kinetics measurements and muscle sympathetic nerve activity recordings in patients with POTS compared with that in controls. The SLC6A2 gene sequence was investigated in leukocytes from POTS patients and healthy controls using single nucleotide polymorphisms genotyping, bisulphite sequencing, and chromatin immunoprecipitation assays for histone modifications and binding of the transcriptional regulatory complex, methyl-CpG binding protein 2. The expression of norepinephrine transporter was lower in POTS patients compared with healthy volunteers. In the absence of altered SLC6A2 gene sequence or promoter methylation, this reduced expression was directly correlated with chromatin modifications. Conclusion—: We propose that chromatin-modifying events associated with SLC6A2 gene suppression may constitute a mechanism of POTS.
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More focused studies attempting to tie genetic variations in the SLC6A2 gene to elevated NE levels have been inconclusive.
“More focused studies attempting to tie genetic variations in the SLC6A2 gene to elevated NE levels, however, have been inconclusive (39,40).”
From Postural Orthostatic Tachycardia Syndrome (2019) · cites this paper as [40]
Another study demonstrated that epigenetic modification of the SCL6A2 gene resulting in its downregulation was more prevalent in POTS patients than in healthy controls.
“Another study demonstrated that epigenetic modification of the SCL6A2 gene resulting in its downregulation was more prevalent in POTS patients than in healthy controls (45).”
From Postural orthostatic tachycardia syndrome: mechanisms and new therapies (2020) · cites this paper as [45]
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Sundarrajan, M., Ravichandran, V., & Ramachandran, R. (2024) · Biosciences Biotechnology Research Asia · doi:10.13005/bbra/3309
In silico analysis of rare pathogenic missense variants in the SLC6A2 gene
Sorokina, M. A., Korshukov, I., & Tursynbek, A. E. (2026) · Medicine and ecology · doi:10.59598/me-2305-6053-2026-118-1-125-133
- Authors
- Bayles, R., KN, H., Lambert, E., Baker, E. K., Agrotis, A., Guo, L., Jowett, J. B. M., Esler, M., Lambert, G., & El-Osta, A.
- Affiliations
- Baker Heart and Diabetes Institute (AU)
- From the Baker IDI Heart & Diabetes Institute (R.B., H.K., E.L., E.K.B., A.A., L.G., J.B.M.J., M.E., G.L., A.E.-O.); and Department of Pathology, The University of Melbourne, and Faculty of Medicine, Nursing and Health Sciences, Monash University (A.E.-O.), Melbourne, Victoria, Australia.
- Venue
- Arteriosclerosis, Thrombosis, and Vascular Biology
- Published
- 2012-08
- Volume
- 32
- Issue
- 8
- Pages
- 1910-1916
- ISSN
- 1079-5642 (ISSN-L)
- 1524-4636
- OpenAlex
- W2138650756
- Cited by
- 56
- References
- 40
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 2 · 2022: 3 · 2021: 2 · 2020: 5 · 2019: 6 · 2018: 3 · 2017: 4 · 2016: 10 · 2015: 4 · 2014: 4 · 2013: 6 · 2012: 2
- FWCI
- 5.21
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Arteriosclerosis Thrombosis and Vascular Biology (publishedVersion)
- PubMed (publishedVersion)
- Swinburne figshare (Swinburne University of Technology) (submittedVersion)
- Topics
- Health Sciences › Medicine › Surgery › Cardiovascular Syncope and Autonomic Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Rate Variability and Autonomic Control
- Keywords
- postural orthostatic tachycardia syndrome, norepinephrine transporter, epigenetic regulation, chromatin modification, histone modifications, DNA methylation, MeCP2, muscle sympathetic nerve activity, head-up tilt, sympathetic nervous system, gene expression inhibition
- MeSH terms
- Adult, Female, Hemodynamics, Humans, Male, Polymorphism, Genetic, Promoter Regions, Genetic, DNA Methylation, Gene Expression Profiling, Epigenesis, Genetic, Norepinephrine Plasma Membrane Transport Proteins, Postural Orthostatic Tachycardia Syndrome
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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