title: Orthostatic intolerance is not necessarily related to a specific mutation (Ala457Pro) in the human norepinephrine transporter gene.
abstract: BACKGROUND
  Orthostatic intolerance (OI) is a syndrome characterized by lightheadedness, palpitations, fatigue, blurred vision, dizziness, chest discomfort, cognitive impairment, and occasionally syncope. These symptoms usually occur after upright posture and are associated with tachycardia and high plasma concentrations of norepinephrine. It has been proposed that a mutation in exon 9 of the norepinephrine transporter gene (Ala457Pro), resulting in more than 98% loss of function compared with the wild type, might provide a pathogenetic mechanism to explain the clinical symptoms of patients with OI.
  
  
  METHODS
  We studied 46 young men from military service who had sought medical advice because of dizziness while standing. Every patient underwent a tilt-table test, with monitoring of blood pressure, heart rate, and plasma catecholamines in supine position and during 30 minutes of standing. Fourteen patients showing the full-blown OI syndrome (30 bpm increase in heart rate and 600 pg/mL plasma norepinephrine levels while standing) underwent direct DNA sequencing of exon 9 of the norepinephrine-transporter gene.
  
  
  CONCLUSIONS
  The specific mutation (Ala457Pro) was not detected in any of the 14 OI patients. Based on these findings, we doubt that this specific genetic transport defect is a frequent cause of the impaired uptake of norepinephrine in OI patients. Its routine determination will therefore not be helpful to establish the clinical diagnosis of OI.
authors.affiliation: Division of Occupational Medicine, University of Vienna, Austria. sabine.ivancsits@akh-wien.ac.at
authors.forename: Sabine
authors.initials: S
authors.lastname: Ivancsits
authors.forename: Arthur
authors.initials: A
authors.lastname: Heider
authors.forename: Hugo W
authors.initials: HW
authors.lastname: Rüdiger
authors.forename: Robert
authors.initials: R
authors.lastname: Winker
mesh_terms: D000293:Adolescent; D000328:Adult; D001794:Blood Pressure / Q000502:physiology; D005091:Exons; D006801:Humans; D007024:Hypotension, Orthostatic / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D009638:Norepinephrine / Q000378:metabolism; D050484:Norepinephrine Plasma Membrane Transport Proteins; D017354:Point Mutation; D017422:Sequence Analysis, DNA; D027981:Symporters / Q000235:genetics* / Q000378:metabolism
chemical_list: D050484:Norepinephrine Plasma Membrane Transport Proteins; C493227:SLC6A2 protein, human; D027981:Symporters; D009638:Norepinephrine