title: Do LQTS gene single nucleotide polymorphisms alter QTc intervals at rest and during exercise stress testing?
abstract: BACKGROUND
  The impact of harboring, genetic variants or single nucleotide polymorphisms (LQT-PM) on the repolarization response during exercise and recovery is unknown.
  
  
  OBJECTIVE
  To assess the QTc interval adaptation during exercise stress testing (EST) in children with LQT polymorphisms compared to a group of age and gender matched normal controls.
  
  
  METHODS
  One hundred forty-eight patients were age and gender matched into two groups: LQT-PM and control. Each patient underwent a uniform exercise protocol employing a cycle ergometer followed by a 9 minute recovery phase with continuous 12-lead electrocardiogram (ECG) monitoring. Intervals (RR, QT and QTc) at rest (supine), peak exercise and in recovery (1, 3, 5, 7, and 9 minutes) were measured.
  
  
  RESULTS
  Forty-three patients were positive for LQT-PM and the control group consisted of 105 patients. A total of 83 SNPs were identified: SCN5A n = 31 (37%), KCNE1 n = 29 (35%), KCNH2 n = 20 (24%), KCNQ1 n = 2 (2%) and KCNE2 n = 1 (1%). The QTc interval measurements of the LQT-PM were longer at rest, peak exercise and all phases of recovery when compared to the control group. Neither group demonstrated abnormal QTc interval adaptation in response to exercise. Patients with homozygous SNPs had longer resting QTc intervals when compared to patients with only heterozygous SNPs (435 ± 23 ms vs. 415 ± 20 ms, respectively, P value <0.006).
  
  
  CONCLUSIONS
  Individuals with LQT-PM may have longer QTc intervals at rest as well as at peak exercise and all phases of the recovery period compared to normal controls. Additionally, subjects with homozygous SNPs had longer resting QTc intervals when compared to those with only heterozygous SNPs.
authors.affiliation: Cleveland Clinic Foundation, Department of Pediatric Cardiology and the Cleveland Clinic Lerner College of Medicine, Cleveland, OH, USA. azizp@ccf.org
authors.forename: Peter F
authors.initials: PF
authors.lastname: Aziz
authors.forename: Tammy S
authors.initials: TS
authors.lastname: Wieand
authors.forename: Jamie
authors.initials: J
authors.lastname: Ganley
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Henderson
authors.forename: Michael
authors.initials: M
authors.lastname: McBride
authors.forename: Maully J
authors.initials: MJ
authors.lastname: Shah
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D000072237:ERG1 Potassium Channel; D004562:Electrocardiography; D051638:Ether-A-Go-Go Potassium Channels / Q000235:genetics; D005080:Exercise Test; D005260:Female; D006720:Homozygote; D006801:Humans; D051657:KCNQ1 Potassium Channel / Q000235:genetics; D008133:Long QT Syndrome / Q000235:genetics* / Q000503:physiopathology*; D008297:Male; D062554:NAV1.5 Voltage-Gated Sodium Channel / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D024642:Potassium Channels, Voltage-Gated / Q000235:genetics; D012146:Rest; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; C489622:KCNE1 protein, human; C489619:KCNE2 protein, human; C000606913:KCNH2 protein, human; D051657:KCNQ1 Potassium Channel; C496909:KCNQ1 protein, human; D062554:NAV1.5 Voltage-Gated Sodium Channel; D024642:Potassium Channels, Voltage-Gated; C568320:SCN5A protein, human