Key result
In patients with dilated cardiomyopathy, CACNG8 mRNA and protein levels were down-regulated and inversely correlated with left ventricular ejection fraction (r = -0.78).
Case-Control (n=23)
Effect estimate: r = -0.78
p-value: p=<0.01
Up-regulation of KCNN3 and KCNJ2 and down-regulation of CACNG8 are associated with left ventricular dysfunction and sustained monomorphic ventricular tachycardia in patients with dilated cardiomyopathy.
May warrant exploration as biomarker or target in dilated cardiomyopathy; leaves open causal role in LV dysfunction and VT.
AIMS: Disruptions in cardiac ion channels have shown to influence the impaired cardiac contraction in heart failure. We sought to determine the altered gene expression profile of this category in dilated cardiomyopathy (DCM) patients and relate the altered gene expression with the clinical signs present in our patients, such as ventricular dysfunction and sustained monomorphic ventricular tachycardia (SMVT). METHODS AND RESULTS: Left ventricular (LV) tissue samples were used in RNA-sequencing technique to elucidate the transcriptomic changes of 13 DCM patients compared to controls (n = 10). We analyzed the differential gene expression of cardiac ion channels, and we found a total of 34 altered genes. We found that the calcium channel CACNG8 mRNA and protein levels were down-regulated and highly and inversely related with LV ejection fraction (LVEF) (r = -0.78, P<0.01). Furthermore, the potassium channels KCNN3 and KCNJ2 mRNA and protein levels were up-regulated and showed also a significant and inverse correlation with LVEF (r = -0.61, P<0.05; r = -0.60, P<0.05) in patients with SMVT. CONCLUSION: A broad set of deregulated genes have been identified by RNA-sequencing technique. The relationship of CACNG8, KCNN3 and KCNJ2 with LVEF, and the up-regulation of KCNN3 and KCNJ2 in all patients with SMVT, irrespective of CACNG8 expression, suggest a significant role for these three ion flux related genes in the LV dysfunction present in this cardiomyopathy and an important relationship between KCNN3 and KCNJ2 up-regulation and the presence of SMVT.
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Ortega et al. (2015) conducted a case-control in Dilated cardiomyopathy (n=23). Dilated cardiomyopathy vs. Non-diseased donor hearts was evaluated on Correlation between CACNG8 mRNA levels and left ventricular ejection fraction (r = -0.78, p=<0.01). In patients with dilated cardiomyopathy, CACNG8 mRNA and protein levels were down-regulated and inversely correlated with left ventricular ejection fraction (r = -0.78).
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