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A screen of candidate genes and influence of beta2-adrenergic receptor genotypes in postural tachycardia syndrome. Auton Neurosci 2005 Jun 15;120(1-2):97-103 PMID: 15946904

Pubmed ID



OBJECTIVE: To screen candidate genes, encoding beta2-adrenergic receptor (beta2AR), alpha2C-adrenergic receptor (alpha(2C)AR), norepinephrine transporter (NET), and mitochondrial complex I (COI), for common single nucleotide polymorphisms (SNPs) in patients with postural tachycardia syndrome (POTS); alterations could potentially cause or aggravate orthostatic tachycardia and to relate beta2AR SNPs, known to effect venomotor tone, to heart rate (HR) and blood pressure measurements during 10-min head-up tilt.

METHODS: (a) DNA extraction from leukocytes of 29 patients with POTS; (b) Denaturing high performance liquid chromatography analysis to screen for the 12-bp deletion (Del322-325) in alpha(2C)AR and for the alanine to proline mutation at amino acid 457 (Ala457Pro) in NET; (c) Systematic direct sequence analysis to screen for SNPs in beta2AR, NET, and COI.

RESULTS: Three common polymorphisms were abundant in at least one allele in beta2AR resulting in a cysteine to arginine in the 5' promoter region (72% of patients), an arginine to glycine at amino acid-16 (Gly16; 86%), and a glutamine to glutamic acid at amino acid-27 (Glu27; 66%), a frequency that was no different to the normal Caucasian population. Orthostatic HR was significantly greater in patients with Glu27. Diastolic blood pressure (DBP) was significantly lower in a subset of patients with Gly16 whose HR were > or =120 beats/min with head-up tilt. All patients did not show the Ala457Pro mutation of NET; all sequence variants detected in alpha(2C)AR, NET, and COI were not considered causally related to POTS.

CONCLUSIONS: Of the candidate genes screened, none harbored a SNP considered to be causally related to POTS. There was significant association of HR and DBP with SNPs of the gene encoding beta2AR; Gly16 or Glu27 could aggravate orthostatic tachycardia by excessive venous pooling.

Author List

Nickander KK, Carlson PJ, Urrutia RA, Camilleri M, Low PA


Raul A. Urrutia MD Center Director, Professor in the Surgery department at Medical College of Wisconsin


2-s2.0-21444433818   13 Citations

MESH terms used to index this publication - Major topics in bold

Blood Pressure
Electron Transport Complex I
Genetic Testing
Heart Rate
Middle Aged
Norepinephrine Plasma Membrane Transport Proteins
Polymorphism, Single Nucleotide
Receptors, Adrenergic, beta-2
jenkins-FCD Prod-332 f92a19b0ec5e8e1eff783fac390ec127e367c2b5