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

Abstract

IntroductionThe 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 methodsThe 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.ResultsSignificantly 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).ConclusionsThe 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.

Effects of Methadone on Corrected Q-T Interval Prolongation in Critically Ill Children

“…3,17,27 Previous investigators have identified decreased HERG gene expression in adults compared with children. 28 The difference in mRNA expression in these patients was nearly 3-fold. 28 Such decreased expression is thought to be an important factor contributing to differences in QTc prolongation between adults and children.…”

“…28 Such decreased expression is thought to be an important factor contributing to differences in QTc prolongation between adults and children. 28 It is currently unknown when HERG gene expression reaches adult levels.…”

KCNQ1 p.L353L affects splicing and modifies the phenotype in a founder population with long QT syndrome type 1

“…Although our sample size of those with the combination p.V205M*p.L353L genotype is small (seven women and five men), the consistently higher increase in QTc in men, above that seen with p.V205M alone is not evident, on average, in the women with the same combination genotype. This finding is of interest in that mechanisms that affect the QTc in men disproportionately are rarely speculated on 50. However, male-specific effect has been observed in studies of modifying variants in LQTS1 populations, such as in the study by Lahtinen et al ,51 where the presence of the variant p.D85N in KCNE1 was shown to modify the QT interval in men with LQTS1, but not in women.…”

Quantitative PCR as an Alternative in the Diagnosis of Long-QT Syndrome

“…The highest mRNA transcript levels of KCNQ1 gene were observed in heart muscle cells; no expression was found in brain, skeletal muscles, or liver. The highest mRNA transcript levels of KCNH2 gene were observed in heart muscle and brain [7]. In the diagnosis of LQTS, as well as in the risk analysis, a lot of aspects such as the measurement of the QT interval, sex, age, clinical characteristics (loss of consciousness, sudden cardiac events, etc.…”

“…The level of KCNQ1 and KCNH2 expression was also compared in a group of adult patients under and over 55 years of age. Among adult patients under 55 years of age a very high number of KCNQ1 mRNA copies and underestimated number of KCNH2 mRNA copies were demonstrated compared to patients above 55 years of age [7]. …”