GNB3 C825T polymorphism is associated with postural tachycardia syndrome in children

Pediatr Int. 2012 Dec;54(6):829-37. doi: 10.1111/j.1442-200X.2012.03707.x. Epub 2012 Nov 21.


Aim: Postural tachycardia syndrome (POTS) is one of the most frequent forms of chronic orthostatic intolerance in children and adolescents. The aim of the present study was to examine the influence of a genetic background on POTS.

Methods: A total of 96 children and adolescents with orthostatic dysregulation were studied. The polymorphism of the G protein β3 subunit (GNB3) C825T and G protein α subunit (GNAS1) T131C of genes encoding components of the autonomic nervous system were determined and compared with circulatory responses to active standing.

Results: In the GNB3 gene C825T polymorphism, the CT and TT genotype had a significant lower supine heart rate and a larger increase of heart rate by standing than the CC, associated with evaluated power of the high-frequency component of heart rate variability. According to the criteria of the Japanese clinical guidelines, 48 children were diagnosed as POTS and 30 were as normal responder with somatoform disorder (SD). In GNB3 C825T polymorphism, the TT genotype was more frequently found in the POTS group (45.8%) than in the SD group (20.0%; P = 0.036) [corrected]. In the GNAS1 T393C, the genotype frequencies for the T393C polymorphisms of GNA1 did not differ significantly between the groups.

Conclusion: The gene polymorphisms GNB3 C825T might be a risk factor for POTS through the enhanced vagal withdrawal of the heart in children and adolescents.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Alleles
  • DNA / genetics*
  • Female
  • Follow-Up Studies
  • Gene Frequency
  • Genetic Predisposition to Disease*
  • Genotype
  • Heart Rate
  • Heterotrimeric GTP-Binding Proteins / genetics*
  • Heterotrimeric GTP-Binding Proteins / metabolism
  • Humans
  • Male
  • Polymorphism, Genetic*
  • Postural Orthostatic Tachycardia Syndrome / genetics*
  • Postural Orthostatic Tachycardia Syndrome / metabolism
  • Postural Orthostatic Tachycardia Syndrome / physiopathology
  • Retrospective Studies
  • Vagus Nerve / physiopathology*


  • G-protein beta3 subunit
  • DNA
  • Heterotrimeric GTP-Binding Proteins