Relationship of common candidate gene variants to electrocardiographic T-wave peak to T-wave end interval and T-wave morphology parameters.
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.
Porthan
Kimmo
K
Department of Cardiology, Helsinki University Central Hospital, Helsinki, Finland. kimmo.porthan@fimnet.fi
Marjamaa
Annukka
A
Viitasalo
Matti
M
Väänänen
Heikki
H
Jula
Antti
A
Toivonen
Lauri
L
Nieminen
Markku S
MS
Newton-Cheh
Christopher
C
Salomaa
Veikko
V
Kontula
Kimmo
K
Oikarinen
Lasse
L
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
D048868:Adaptor Proteins, Signal Transducing; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; C000606913:KCNH2 protein, human; C488081:NOS1AP protein, human