Aims: To determine the genetic variability of long QT syndrome (LQTS)-associated genes (KCNQ1, HERG, KCNE1 and KCNE2) among three distinct ethnic groups in the Singapore population.
Methods: Genomic DNA samples from up to 265 normal healthy Chinese, 118 Malay and 139 Indian volunteer subjects were screened for genetic variations in the coding region of the LQTS-associated genes using denaturing high-performance liquid chromatography and sequencing analyses.
Results: In total, 37 single nucleotide polymorphisms (SNPs) were identified in the coding exons of the LQTS-associated potassium ion channel genes, seven of which were novel nonsynonymous polymorphisms. SNPs 356G-->A (exon 1 of KCNQ1), 2624C-->T and 2893G-->A (exon 11 of HERG), 3164G-->A, 3322C-->G and 3460G-->A (exon 14 of HERG), and 79C-->T (exon 3 of KCNE2) resulted in Gly119Asp, Thr875Met, Gly965Arg, Arg1055Gln, Leu1108Val, Gly1154Ser and Arg27Cys amino acid substitutions, respectively. In addition, 16 intronic variants were detected. The functional consequence of these variants has not been studied and their association with risk of LQTS is unclear.
Conclusions: There exist multiple genetic polymorphisms of the LQTS-associated genes in the three distinct Asian populations. Though the functional significance of many of these SNPs is unknown, this interindividual and interethnic genetic variability may underlie the different susceptibilities of individuals to developing LQTS.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1885019 | PMC |
| http://dx.doi.org/10.1111/j.1365-2125.2005.02545.x | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Unraveling Complexities in Genetically Elusive Long QT Syndrome.
Circ Arrhythm Electrophysiol
February 2024
Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD.
Article Synopsis
- Genetic testing is essential for diagnosing long QT syndrome (LQTS) and can provide valuable information for patients and their families, but about 25% of patients show no identifiable genetic variants despite having significant symptoms.
- The prognosis for these patients mirrors that of those with known genetic variants, highlighting the need to investigate various potential causes of QT interval prolongation beyond genetic factors, including environmental influences and exercise-related issues.
- Continuous advancements in genetics may reveal new risk factors and causal genes for LQTS, emphasizing the importance of expert cardiogenetic clinics in effectively managing and counseling affected patients, especially those with unclear genetic test results.
Prediction of Kv11.1 potassium channel PAS-domain variants trafficking via machine learning.
J Mol Cell Cardiol
July 2023
Stritch School of Medicine, Loyola University Chicago, Maywood, IL, USA. Electronic address:
Congenital long QT syndrome (LQTS) is characterized by a prolonged QT-interval on an electrocardiogram (ECG). An abnormal prolongation in the QT-interval increases the risk for fatal arrhythmias. Genetic variants in several different cardiac ion channel genes, including KCNH2, are known to cause LQTS.
View Article and Find Full Text PDFPhenotypes of Overdiagnosed Long QT Syndrome.
J Am Coll Cardiol
February 2023
Windland Smith Rice Sudden Death Genomics Laboratory, Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, Minnesota, USA; Division of Pediatric Cardiology, Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, Minnesota, USA; Division of Heart Rhythm Services, Windland Smith Rice Genetic Heart Rhythm Clinic, Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota, USA. Electronic address:
Background: Long QT syndrome (LQTS) predisposes individuals to arrhythmic syncope or seizure, sudden cardiac arrest, or sudden cardiac death (SCD). Increased physician and public awareness of LQTS-associated warning signs and an increase in electrocardiographic screening programs may contribute to overdiagnosis of LQTS.
Objectives: This study sought to identify the diagnostic miscues underlying the continued overdiagnosis of LQTS.
Mutation-Specific Differences in Kv7.1 () and Kv11.1 () Channel Dysfunction and Long QT Syndrome Phenotypes.
Int J Mol Sci
July 2022
Department of Physiology, College of Medicine, University of Kentucky, Lexington, KY 40536, USA.
The electrocardiogram (ECG) empowered clinician scientists to measure the electrical activity of the heart noninvasively to identify arrhythmias and heart disease. Shortly after the standardization of the 12-lead ECG for the diagnosis of heart disease, several families with autosomal recessive (Jervell and Lange-Nielsen Syndrome) and dominant (Romano-Ward Syndrome) forms of long QT syndrome (LQTS) were identified. An abnormally long heart rate-corrected QT-interval was established as a biomarker for the risk of sudden cardiac death.
View Article and Find Full Text PDFAlterations of Nedd4-2-binding capacity in PY-motif of Na 1.5 channel underlie long QT syndrome and Brugada syndrome.
Acta Physiol (Oxf)
June 2020
Department of Cardiovascular Medicine, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, P. R. China.
Aims: Pathogenic variants of the SCN5A gene can cause Brugada syndrome (BrS) and long QT syndrome (LQTS), which predispose individuals to potentially fatal ventricular arrhythmias and sudden cardiac death. SCN5A encodes the Na 1.5 protein, the pore forming α-subunit of the voltage-dependent cardiac Na channel.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!