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. 2010 Jul;7(7):898-903.
doi: 10.1016/j.hrthm.2010.03.002. Epub 2010 Mar 4.

Relationship of common candidate gene variants to electrocardiographic T-wave peak to T-wave end interval and T-wave morphology parameters

Kimmo Porthan  1 , Annukka Marjamaa, Matti Viitasalo, Heikki Väänänen, Antti Jula, Lauri Toivonen, Markku S Nieminen, Christopher Newton-Cheh, Veikko Salomaa, Kimmo Kontula, Lasse Oikarinen
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Relationship of common candidate gene variants to electrocardiographic T-wave peak to T-wave end interval and T-wave morphology parameters

Kimmo Porthan et al. Heart Rhythm. 2010 Jul.

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.

Conclusion: 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.

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Figures

Figure 1
Figure 1
Effect of KCNH2 K897T, KCNH2 rs3807375, and NOS1AP 10918594 SNPs on electrocardiographic QTpeak, QTend, and TPE interval. Values are differences from major homozygotes per one minor allele. Because of similarity of the results for all other NOS1AP SNPs, results are shown only for rs10918594. *P<.05, †P<.01, ‡P<.0001. Nc=nomogram-corrected for heart rate, n.s.=nonsignificant, SNP=single-nucleotide polymorphism, TPE=T-wave peak to T-wave end.
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