Age-and sex-dependent mRNA expression of KCNQ1 and HERG in patients with long QT syndrome type 1 and 2

Introduction: The main goal of this study was to examine the patient age and sex dependent expression of KCNQ1 and HERG genes that encode potassium channels responsible for the occurrence of long QT syndrome (LQTS).

Material and methods: The study enrolled 43 families whose members suffered from LQTS type 1 (LQTS1) or 2 (LQTS2) or were healthy. The study attempted to prove that β-actin is a good endogenous control when determining the expression of the studied genes. Examination of gene expression was achieved with quantitative real-time PCR (QRT-PCR). Expression of the investigated genes was inferred from the analysis of the number of mRNA copies per 1 μg total RNA isolated from whole blood.

Results: Significantly lower KCNQ1 and KCNH2 mRNA levels in healthy females than healthy males were observed (p = 0.032; p = 0.02). In male patients both transcripts were expressed at a lower level (p = 0.0084; p = 0.035). The comparison of transcriptional activity of KCNQ1 and KCNH2 in healthy adults and children revealed higher KCNQ1 and lower KCNH2 mRNA levels in healthy adults (p = 0.033; p = 0.04), higher KCNQ1 and lower KCNH2 mRNA levels in adult patients below 55 years old than in adults over 55 years old (p=0.036; p = 0.044), and significantly higher KCNQ1 and lower KCNH2 mRNA levels in adult patients (over 55 years) than in paediatric patients (below 15 years) (p=0.047; p = 0.08).

Conclusions: The results support the hypothesis that KCNQ1 and HERG gene expression is influenced by age and gender in human patients with long QT syndrome and in healthy subjects.