title: Beta1-adrenergic receptor polymorphisms, QTc interval and occurrence of symptoms in type 1 of long QT syndrome.
abstract: BACKGROUND
  The most prevalent LQT1 form of inherited long QT syndrome is caused by mutations of the KCNQ1 gene resulting repolarizing I(Ks) potassium current to decrease and the QT interval to prolong. As abrupt sympathetic activation triggers ventricular arrhythmias that may cause syncopal attacks and sudden death in LQT1 patients, we investigated whether two known beta1-adrenergic receptor polymorphisms were associated with the duration of QT interval or history of symptoms in LQT1.
  
  
  METHODS
  We determined beta1-adrenergic receptor polymorphisms (Ser49Gly and Arg389Gly) in 168 LQT1 patients. We also reviewed each patient's clinical records on the history of long QT syndrome-related symptoms and measured QT intervals from baseline ECG in each subject and from an exercise test ECG in 55 LQT1 patients.
  
  
  RESULTS
  Patients with the homozygous Arg389Arg genotype tended to have shorter and those with the Ser49Ser genotype longer QT intervals than patients with other genotypes, but neither polymorphism studied alone affected the risk of symptoms. In contrast, adjusted odds ratio for the history of symptoms was 4.9 (95% CI 1.18 to 20.3) in patients homozygous for both Ser49 and Arg389. These double homozygous patients showed similar QT intervals as the rest of the LQT1 cohort.
  
  
  CONCLUSIONS
  In this relatively small study, double homozygosity for Arg389 and Ser49 of the human beta1-adrenergic receptor associated with the risk of symptoms in LQT1. The association between these beta1-adrenergic receptor polymorphisms and the symptom history in LQT1 is not mediated via QT interval duration.
authors.affiliation: Department of Medicine, University of Helsinki, 00290 Helsinki, Finland. kristian.paavonen@hus.fi
authors.forename: Kristian J
authors.initials: KJ
authors.lastname: Paavonen
authors.forename: Heikki
authors.initials: H
authors.lastname: Swan
authors.forename: Kirsi
authors.initials: K
authors.lastname: Piippo
authors.forename: Päivi
authors.initials: P
authors.lastname: Laitinen
authors.forename: Heidi
authors.initials: H
authors.lastname: Fodstad
authors.forename: Seppo
authors.initials: S
authors.lastname: Sarna
authors.forename: Lauri
authors.initials: L
authors.lastname: Toivonen
authors.forename: Kimmo
authors.initials: K
authors.lastname: Kontula
authors.forename: Matti
authors.initials: M
authors.lastname: Viitasalo
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004562:Electrocardiography; D005080:Exercise Test; D005260:Female; D005387:Finland / Q000453:epidemiology; D005838:Genotype; D006801:Humans; D051657:KCNQ1 Potassium Channel / Q000235:genetics; D008133:Long QT Syndrome / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D016017:Odds Ratio; D011110:Polymorphism, Genetic / Q000235:genetics*; D018342:Receptors, Adrenergic, beta-1 / Q000235:genetics*; D012016:Reference Values; D012044:Regression Analysis
chemical_list: D051657:KCNQ1 Potassium Channel; C496909:KCNQ1 protein, human; D018342:Receptors, Adrenergic, beta-1