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Dopamine--hydroxylase in postural tachycardia syndrome

¹Autonomic Dysfunction Center and ²Center for Molecular Neuroscience, Vanderbilt University, Nashville, Tennessee

Submitted 20 December 2006 ; accepted in final form 3 April 2007

Norepinephrine is frequently elevated in postural tachycardia syndrome (POTS), a syndrome of heterogeneous etiology characterized by a >30 beats/min increase in heart rate with standing. Norepinephrine is synthesized from dopamine by dopamine--hydroxylase (DBH). The results of a preliminary study suggested that the T allele frequency of the DBH –1021CT polymorphism is elevated in POTS. This allele correlates with low DBH activity and might predict reduced serum DBH activity in patients with POTS. To test the hypothesis that low DBH activity and the underlying –1021CT polymorphism are associated with increased susceptibility to POTS, we measured serum DBH activity in POTS and determined its relationship to the DBH genotype and plasma norepinephrine. Serum DBH was similar for 83 normal volunteers and 42 patients with POTS: median (range) = 22.5 (0.5–94.2) and 19.6 (0.1–68.8) nmol·min^–1·ml^–1, respectively (P = 0.282). The genotype frequencies for 254 control and 157 POTS patients were not different between groups (63% CC genotype and 5% TT genotype, P = 0.319). The T allele associated with lower serum DBH in both groups [control serum DBH = 15.7 (SD 12.3) and 35.1 nmol·min^–1·ml^–1 (SD 18.6) for T carriers and noncarriers, respectively; POTS serum DBH = 8.2 (SD 5.6) and 28.5 nmol·min^–1·ml^–1 (SD 14.7) for T carriers and noncarriers, respectively]. High DBH in POTS was linked to elevated plasma levels of norepinephrine. Although DBH activity and genotype are unlikely to be primary determinants of susceptibility to POTS, differences in DBH activity in POTS may reflect differences in the level of sympathetic activation.

–1021CT; catecholamines