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(Hypertension. 2005;46:1103.)
© 2005 American Heart Association, Inc.

Original Articles

Endothelial NO Synthase Polymorphisms and Postural Tachycardia Syndrome

Emily M. Garland; Robert Winker; Scott M. Williams; Lan Jiang; Krista Stanton; Daniel W. Byrne; Italo Biaggioni; Ingolf Cascorbi; John A. Phillips, III; Paul A. Harris; Hugo Rüdiger; David Robertson

From the Autonomic Dysfunction Center (E.M.G., I.B., D.R.), Division of Cardiovascular Medicine (S.M.W.), Center for Human Genetics Research (S.M.W., L.J.), Division of Medical Genetics (K.S., J.A.P.), Department of Biostatistics (D.W.B.), and Department of Biomedical Engineering (P.A.H.), Vanderbilt University, Nashville, Tenn; Division of Occupational Medicine (R.W., H.R.), Medical University of Vienna, Währinger Gürtel, Austria; and Institute of Pharmacology (I.C.), University Hospital Schleswig Holstein, Kiel, Germany.

Correspondence to Emily M. Garland, PhD, Autonomic Dysfunction Center, AA3228 Medical Center N, Vanderbilt University, Nashville, TN 37232-2195. E-mail emily.garland{at}vanderbilt.edu

Postural tachycardia syndrome (POTS) is a heterogeneous disorder characterized by an excessive rise in heart rate and symptoms consistent with cerebral hypoperfusion in the upright position. NO produced by endothelial NO synthase is a significant factor in the regulation of blood flow. Genetic polymorphisms in the promoter region (T-786C) and exon 7 (E298D) of the NO synthase isoform 3 gene affect enzyme activity and have been associated with a number of cardiovascular diseases. Because some findings in POTS suggest aberrant NO-mediated functions, we postulated that the variant genotypes of these polymorphisms may increase the risk of developing POTS and correlate with more severe symptoms. We genotyped 136 patients with POTS (mean age 32.2±9.9 years; 46 men and 90 women) from Nashville, Tenn, and Vienna, Austria, and compared them with 191 healthy volunteers (mean age 29.1±8.0 years; 127 men and 64 women). Participants also underwent orthostatic testing with blood pressure, heart rate, and plasma norepinephrine measurements while supine and upright. The frequencies of the -786CC and 298DD genotypes were significantly lower in patients with POTS than in control subjects (odds ratio [OR], 0.28; 95% confidence interval [CI], 0.14 to 0.57; P=0.001 for -786CC; and OR, 0.44; 95% CI, 0.21 to 0.91; P=0.033 for 298DD). According to 2-locus genotype analyses, patients with -786CC and 298EE or 298ED experienced the largest changes in heart rate and plasma norepinephrine with standing. These results indicate that NO may influence the development of POTS and the severity of POTS symptoms.

Key Words: tachycardia • genetics • nitric oxide • hemodynamics • heart rate • norepinephrine

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