The results of next-generation sequencing in men with borderline QT interval prolongation (pilot study)

Highlights. Probably causal mutations of QT interval prolongation in genes associated with LQTS were found in men of the Siberian population.

Aim. To detect and study mutations in individuals with borderline prolongation of the QT interval in Siberian males.

Methods. The study was conducted on the material of the international project HAPIEE in the period from 2003 to 2005 and screening of young people aged 25–44, performed in Novosibirsk. The total sample of men was 1353 people aged 25 to 69 years. From each age subgroup (25–29, 30–34, ..., 65–69 years old) 2–3 samples with the highest QT values were selected . The study group consisted of 30 men who subsequently underwent sequencing of a panel of genes. The search for mutations was carried out in genes associated with long QT syndrome (LQTS): KCNQ1, KCNH2, SCN5A, KCNE1, KCNE2, KCNJ2, CACNA1, SCN4B, KCNJ5, ANK2, CAV3, SNTA1, AKAP9, CALM1 and CALM2. All identified single nucleotide variants were verified by direct Sanger sequencing.

Results. Three rare variants in the LQTS genes have been identified: p.P197L of the KCNQ1 gene, p.R176W, and p.D1003GfsX116 of the KCNH2 gene.

Conclusion. In Caucasian men from the Novosibirsk population with borderline prolongation of the QT interval, probably causal substitutions in the LQTS genes – KCNH2 and KCNQ1, contributing to the prolongation of the QT interval, were found. To clarify the spectrum and frequency of occurrence of various mutations in genes, life-threatening arrhythmias in the population, additional studies are needed on extended samples.

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