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.

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.

Figure 1

Effect of KCNH2 K897T, KCNH2 rs3807375, and NOS1AP 10918594 SNPs on electrocardiographic QT_peak, QT_end, 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.