title: Relationship of common candidate gene variants to electrocardiographic T-wave peak to T-wave end interval and T-wave morphology parameters.
abstract: BACKGROUND
  Single-nucleotide polymorphisms (SNPs) in genes encoding cardiac ion channels and nitric oxide synthase-1 adaptor protein (NOS1AP) are associated with electrocardiographic (ECG) QT-interval duration, but the association of these SNPs with new, prognostically important ECG measures of ventricular repolarization is unknown.
  
  
  OBJECTIVE
  The purpose of this study was to examine the relationship of SNPs to ECG T-wave peak to T-wave end (TPE) interval and T-wave morphology parameters.
  
  
  METHODS
  We studied 5,890 adults attending the Health 2000 Study, a Finnish epidemiologic survey. TPE interval and four T-wave morphology parameters were measured from digital 12-lead ECGs and related to the seven SNPs showing a phenotypic effect on QT-interval duration in the Health 2000 Study population.
  
  
  RESULTS
  In multivariable analyses, the KCNH2 K897T minor allele was associated with a 1.2-ms TPE-interval shortening (P = .00005) and the KCNH2 intronic rs3807375 minor allele was associated with a 0.8-ms TPE-interval prolongation (P = .001), whereas the KCNE1 D85N variant had no TPE-interval effect (P = .20). NOS1AP minor alleles (rs2880058, rs4657139, rs10918594, rs10494366) were associated with a shorter TPE interval (effects from 0.5 to 0.8 ms, P from .032 to .002), which resulted from their stronger effects on QT(peak) than QT(end) interval. None of the SNPs showed a consistent association with T-wave morphology parameters.
  
  
  CONCLUSIONS
  KCNH2 K897T and rs3807375 as well as the four studied NOS1AP variants have modest effects on ECG TPE interval but are not related to T-wave morphology measures. The previously observed prognostic value of T-wave morphology parameters likely is not based on these SNPs.
authors.affiliation: Department of Cardiology, Helsinki University Central Hospital, Helsinki, Finland. kimmo.porthan@fimnet.fi
authors.forename: Kimmo
authors.initials: K
authors.lastname: Porthan
authors.forename: Annukka
authors.initials: A
authors.lastname: Marjamaa
authors.forename: Matti
authors.initials: M
authors.lastname: Viitasalo
authors.forename: Heikki
authors.initials: H
authors.lastname: Väänänen
authors.forename: Antti
authors.initials: A
authors.lastname: Jula
authors.forename: Lauri
authors.initials: L
authors.lastname: Toivonen
authors.forename: Markku S
authors.initials: MS
authors.lastname: Nieminen
authors.forename: Christopher
authors.initials: C
authors.lastname: Newton-Cheh
authors.forename: Veikko
authors.initials: V
authors.lastname: Salomaa
authors.forename: Kimmo
authors.initials: K
authors.lastname: Kontula
authors.forename: Lasse
authors.initials: L
authors.lastname: Oikarinen
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000328:Adult; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D006329:Heart Conduction System; D006801:Humans; D008133:Long QT Syndrome / Q000235:genetics; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D020641:Polymorphism, Single Nucleotide
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; C000606913:KCNH2 protein, human; C488081:NOS1AP protein, human