A screen of candidate genes and influence of beta2-adrenergic receptor genotypes in postural tachycardia syndrome.
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.
Nickander
Kim K
KK
Department of Neurology, Mayo Clinic and Foundation, 200 First Street SW, Rochester, Minnesota 55905, USA.
Carlson
Paula J
PJ
Urrutia
Raul A
RA
Camilleri
Michael
M
Low
Phillip A
PA
D000328:Adult; D001794:Blood Pressure / Q000235:genetics; D042967:Electron Transport Complex I / Q000235:genetics; D005260:Female; D005820:Genetic Testing; D005838:Genotype; D006339:Heart Rate / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D050484:Norepinephrine Plasma Membrane Transport Proteins; D020641:Polymorphism, Single Nucleotide; D011187:Posture; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics*; D027981:Symporters / Q000235:genetics; D013610:Tachycardia / Q000235:genetics*
D050484:Norepinephrine Plasma Membrane Transport Proteins; D018343:Receptors, Adrenergic, beta-2; C493227:SLC6A2 protein, human; D027981:Symporters; D042967:Electron Transport Complex I