Dataset Information

The KCNE genes in hypertrophic cardiomyopathy: a candidate gene study.

ABSTRACT: BACKGROUND:The gene family KCNE1-5, which encode modulating ?-subunits of several repolarising K+-ion channels, has been associated with genetic cardiac diseases such as long QT syndrome, atrial fibrillation and Brugada syndrome. The minK peptide, encoded by KCNE1, is attached to the Z-disc of the sarcomere as well as the T-tubules of the sarcolemma. It has been suggested that minK forms part of an "electro-mechanical feed-back" which links cardiomyocyte stretching to changes in ion channel function. We examined whether mutations in KCNE genes were associated with hypertrophic cardiomyopathy (HCM), a genetic disease associated with an improper hypertrophic response. RESULTS:The coding regions of KCNE1, KCNE2, KCNE3, KCNE4, and KCNE5 were examined, by direct DNA sequencing, in a cohort of 93 unrelated HCM probands and 188 blood donor controls.Fifteen genetic variants, four previously unknown, were identified in the HCM probands. Eight variants were non-synonymous and one was located in the 3'UTR-region of KCNE4. No disease-causing mutations were found and no significant difference in the frequency of genetic variants was found between HCM probands and controls. Two variants of likely functional significance were found in controls only. CONCLUSIONS:Mutations in KCNE genes are not a common cause of HCM and polymorphisms in these genes do not seem to be associated with a propensity to develop arrhythmia.

SUBMITTER: Hedley PL

PROVIDER: S-EPMC3204304 | biostudies-literature | 2011 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

The KCNE genes in hypertrophic cardiomyopathy: a candidate gene study.

Hedley Paula L PL Haundrup Ole O Andersen Paal S PS Aidt Frederik H FH Jensen Morten M Moolman-Smook Johanna C JC Bundgaard Henning H Christiansen Michael M

Journal of negative results in biomedicine 20111003

<h4>Background</h4>The gene family KCNE1-5, which encode modulating β-subunits of several repolarising K+-ion channels, has been associated with genetic cardiac diseases such as long QT syndrome, atrial fibrillation and Brugada syndrome. The minK peptide, encoded by KCNE1, is attached to the Z-disc of the sarcomere as well as the T-tubules of the sarcolemma. It has been suggested that minK forms part of an "electro-mechanical feed-back" which links cardiomyocyte stretching to changes in ion chan ...[more]

PMID: 21967835

Similar Datasets

Project description:BackgroundConsidering it is one of the major causes of sudden cardiac arrest, the proper management of hypertrophic cardiomyopathy (HCM) is essential. However, efficient treatment options for this disease are still lacking. The discovery of HCM-associated hub genes may help in diagnosis and offer a reliable tool for developing effective therapeutic strategies.MethodsWe examined HCM-based gene expression datasets (GSE36961) from the Gene Expression Omnibus (GEO) database for the identification of differentially expressed genes (DEGs), PPI network development, module screening, and shortlisting of hub genes via GEOR2, STRING, and Cytoscape. Moreover, we also used another HCM-based gene expression dataset (GSE32453) for the expression validation of hub genes. Following this, we constructed the lncRNA-cricRNA-miRNA-mRNA regulatory network after retrieving information from the miRTarBase, miRDB, and MiRcode databases. Finally, we used DAVID to perform functional and pathway analysis of the hub genes.ResultsFrom GSE36961, a total of the 262 most significant DEGs, including 162 down-regulated and 76 up-regulated, were identified between HCM patients and normal individuals. Among these DEGs, a total of 10 significantly down-regulated DEGs, including cluster of differentiation 14 (CD14), beta2 Integrin Gene (ITGB2), C1q subcomponent subunit B (C1QB), Cluster of Differentiation 163 (CD163), Hematopoietic Cell-Specific Lyn Substrate 1 (HCLS1), Arachidonate 5-Lipoxygenase Activating Protein (ALOX5AP), Pleckstrin (PLEK), Complement C1q C Chain (C1QC), Fc fragment Of IgE receptor Ig (FCER1G), and tyrosine kinase binding protein (TYROBP), were shortlisted as the hub genes. Pathway enrichment analysis showed that the identified hub genes were involved in the dysregulation of some diverse pathways in HCM patients. Such as, Pertussis, Complement and coagulation cascade, Legnionellosis, Asthma, Staphylococcus aureus infection, etc. Lastly, we also explored hub genes' regulatory 2 MicroRNAs (miRNAs, has-mir-7-5p and has-mir-27a-3p), one Long non-coding RNAs (lncRNA, OIP5-AS1-201), and one Circular RNA (cricRNA, CDR1as) via lncRNA-cricRNA-miRNA-mRNA regulatory network.ConclusionOur study revealed that ten hub genes (CD14, ITGB2, C1QB, CD163, HCLS1, ALOX5AP, PLEK, C1QC, FCER1G, and TYROBP) are involved in the development and progression of HCM. These genes can potentially be used as biomarkers and therapeutic targets for HCM patients.

Dataset Information

The KCNE genes in hypertrophic cardiomyopathy: a candidate gene study.

Publications

The KCNE genes in hypertrophic cardiomyopathy: a candidate gene study.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets