In-Depth Look into Genetic Influences on Postural Orthostatic Tachycardia Syndrome and Ehlers-Danlos Syndrome: A Comprehensive Review

Mouliprabakaran Sundarrajan, Venkatesaprasath Ravichandran and Revanth Ramachandran

Department of Pharmacy Practice, J.K.K.Nattraja College of Pharmacy, Kumarapalayam, Tamil Nadu.

Corresponding Author E-mail:revram95@gmail.com

ABSTRACT: Postural Orthostatic Tachycardia Syndrome (POTS) is a prevalent but underrecognized cardiovascular autonomic disorder characterized by an excessive heart rate increase upon standing and symptoms of orthostatic intolerance. Predominantly affecting women aged 15–45, POTS can be debilitating and economically burdensome, particularly impacting young adults in their prime educational and professional years. The etiology of POTS remains elusive, with both genetic and non-genetic factors, such as trauma, infections, and pregnancy, potentially contributing. Genetic mutations have been implicated,particularly in the norepinephrine transporter (NET) gene. NET plays a critical role in norepinephrine reuptake, and its dysfunction can lead to heightened sympathetic nervous system activity, contributing to POTS symptoms. Specific polymorphisms, like rs7194256 in the NET gene, have been linked to impaired norepinephrine clearance and increased sympathetic activity. Epigenetic modifications and regulatory mechanisms involving transcription factors and microRNAs also influence NET gene expression. Additionally, conditions like Ehlers-Danlos Syndrome (EDS) often coexist with POTS, suggesting a complex interplay between connective tissue disorders and autonomic dysfunction. While the genetic basis of POTS, including the role of NET gene variations, is not fully understood, preliminary evidence suggests these variations may affect norepinephrine modulation and autonomic function. Further research with larger, more diverse cohorts and advanced genetic analyses is needed to elucidate the mechanisms by which NET gene variations contribute to POTS. Understanding these mechanisms could improve diagnostic and therapeutic strategies, ultimately enhancing patient outcomes.

KEYWORDS: Ala457Pro mutation; genetic polymorphisms; genetic connective tissue disorders; norepinephrine transporter (NET) gene; SLC6A2 gene

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