What is the clinical evidence from this study?

Study design: Case-Control. Population: Dilated Cardiomyopathy (n=29). Intervention: Dilated cardiomyopathy vs. Non-diseased donor hearts. Primary outcome: Gene expression of SCN2B (Fold change 2.03, p=<0.0001).

December 5, 2013Open Access

Differential Gene Expression of Cardiac Ion Channels in Human Dilated Cardiomyopathy

Q: What are the key findings of this study?

Dilated cardiomyopathy is associated with differential expression of cardiac ion channel genes, including significant upregulation of SCN2B and downregulation of KCNJ5, KCNJ8, CLIC2, and CACNB2.

Resultado clave

Dilated cardiomyopathy is associated with differential expression of cardiac ion channel genes, including significant upregulation of SCN2B and downregulation of KCNJ5, KCNJ8, CLIC2, and CACNB2.

Diseño del estudio

Tipo

Case-Control (n=29)

Multicéntrico

PICO estructurado

Población

29 left ventricular tissue samples from patients with end-stage non-ischemic dilated cardiomyopathy undergoing cardiac transplantation and non-diseased control donors.

Comparador

Control donors

Resultado

Differential gene expression of 7 cardiac ion channel genessurrogate

Significant alterations in the expression of cardiac ion channel genes in patients with dilated cardiomyopathy may contribute to systolic contractile dysfunction and offer new therapeutic targets.

Resultado numérico

Estimación del efecto: Fold change 2.03

valor p: p=<0.0001

Limitaciones

High variability in disease etiology and treatment among end-stage failing human hearts.
Patients were on conventional therapy which may influence ion channel mRNA levels.
Tissue samples were confined to the transmural left ventricle apex, limiting generalizability to all layers and regions of the left ventricle.

Resumen

BACKGROUND: Dilated cardiomyopathy (DCM) is characterized by idiopathic dilation and systolic contractile dysfunction of the cardiac chambers. The present work aimed to study the alterations in gene expression of ion channels involved in cardiomyocyte function. METHODS AND RESULTS: Microarray profiling using the Affymetrix Human Gene® 1.0 ST array was performed using 17 RNA samples, 12 from DCM patients undergoing cardiac transplantation and 5 control donors (CNT). The analysis focused on 7 cardiac ion channel genes, since this category has not been previously studied in human DCM. SCN2B was upregulated, while KCNJ5, KCNJ8, CLIC2, CLCN3, CACNB2, and CACNA1C were downregulated. The RT-qPCR (21 DCM and 8 CNT samples) validated the gene expression of SCN2B (p < 0.0001), KCNJ5 (p < 0.05), KCNJ8 (p < 0.05), CLIC2 (p < 0.05), and CACNB2 (p < 0.05). Furthermore, we performed an IPA analysis and we found a functional relationship between the different ion channels studied in this work. CONCLUSION: This study shows a differential expression of ion channel genes involved in cardiac contraction in DCM that might partly underlie the changes in left ventricular function observed in these patients. These results could be the basis for new genetic therapeutic approaches.

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