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Interaction of genetic predisposition and environmental factors in the pathogenesis of idiopathic orthostatic intoleranceBACKGROUND: The hemodynamic and autonomic abnormalities in idiopathic orthostatic intolerance (IOI) have been studied extensively. However, the mechanisms underlying these abnormalities are not understood. If genetic predisposition were important in the pathogenesis of IOI, monozygotic twins of patients with IOI should have similar hemodynamic and autonomic abnormalities. METHODS: We studied two patients with IOI and their identical twins. Both siblings in the first twin pair had orthostatic symptoms, significant orthostatic tachycardia, increased plasma norepinephrine levels with standing, and a greater than normal decrease in systolic blood pressure with trimethaphan infusion. RESULTS: Both siblings had a normal response of plasma renin activity to upright posture. In the second twin pair, only one sibling had symptoms of orthostatic intolerance, an orthostatic tachycardia, and raised plasma catecholamines with standing. The affected sibling had inappropriately low plasma renin activity with standing and was 8-fold more sensitive to the pressor effect of phenylephrine than the unaffected sibling. CONCLUSIONS: We conclude that in some patients, IOI seems to be strongly influenced by genetic factors. In others, however, IOI may be mainly caused by nongenetic factors. These findings suggest that IOI is heterogenous, and that both genetic and environmental factors contribute individually or collectively to create the IOI phenotype.
Document ID
20040141776
Acquisition Source
Legacy CDMS
Document Type
Reprint (Version printed in journal)
Authors
Jordan, J.
(Clinical Research Center, Franz Volhard Clinic at the Max Delbrueck Centrum Berlin, Germany)
Shannon, J. R.
Jacob, G.
Pohar, B.
Robertson, D.
Date Acquired
August 22, 2013
Publication Date
November 1, 1999
Publication Information
Publication: The American journal of the medical sciences
Volume: 318
Issue: 5
ISSN: 0002-9629
Subject Category
Aerospace Medicine
Funding Number(s)
CONTRACT_GRANT: 1PO1-HL56693
CONTRACT_GRANT: 1UO1-NS33460
CONTRACT_GRANT: RR00095
Distribution Limits
Public
Copyright
Other
Keywords
NASA Discipline Regulatory Physiology
Non-NASA Center
Case Reports
Twin Study
NASA Program Biomedical Research and Countermeasures

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