Interaction of genetic predisposition and environmental factors in the pathogenesis of idiopathic orthostatic intolerance.
BACKGROUND
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.
Jordan
J
J
Clinical Research Center, Franz Volhard Clinic at the Max Delbrueck Centrum, Berlin, Germany.
Shannon
J R
JR
Jacob
G
G
Pohar
B
B
Robertson
D
D
D000328:Adult; D000959:Antihypertensive Agents; D001341:Autonomic Nervous System / Q000503:physiopathology*; D004200:Diseases in Twins; D004777:Environment; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007024:Hypotension, Orthostatic / Q000097:blood / Q000209:etiology* / Q000235:genetics / Q000503:physiopathology; D018733:Nicotinic Antagonists; D009638:Norepinephrine / Q000097:blood; D011187:Posture; D013575:Syncope / Q000097:blood / Q000209:etiology* / Q000235:genetics / Q000503:physiopathology; D013610:Tachycardia / Q000097:blood / Q000209:etiology* / Q000235:genetics / Q000503:physiopathology; D014294:Trimethaphan
D000959:Antihypertensive Agents; D018733:Nicotinic Antagonists; D014294:Trimethaphan; D009638:Norepinephrine