Quantitative analysis of circulating cell-free mitochondrial DNA in plasma of children with primary carnitine deficiency-associated cardiomyopathy and its clinical significance / 中华实用儿科临床杂志

ABSTRACT

Objective:To detect the level of the circulating cell-free mitochondrial DNA (ccf-mtDNA) in plasma of children with primary carnitine deficiency (PCD)-associated cardiomyopathy and evaluate its clinical significance.Methods:In this prospective case-control study, peripheral blood samples were collected from 7 PCD patients with cardiomyopathy (PCD group), 16 dilated cardiomyopathy (DCM) patients (DCM group), and 50 healthy children (healthy control group) in the Pediatric Cardiovascular Department Ward of First Hospital of Jilin University from July 2017 to June 2022.The ccf-mtDNA levels were measured and compared between groups by the real-time fluorescence quantitative polymerase chain reaction.The correlations between plasma ccf-mtDNA level and blood free carnitine level and cardiac function in the PCD group were analyzed.The changes in the ccf-mtDNA level were monitored after L-carnitine treatment in the PCD group.The Kruskal-Wallis test was used for comparison among the three groups.The Mann-Whitney test was used for comparison between the PCD group and the control group.Changes before and after treatment in the PCD group were analyzed using the paired Wilcoxon rank sum test.The correlation between variables was evaluated by Logistic regression.Results:The plasma ccf-mtDNA levels in the PCD and DCM groups were 3.69×10 6 (1.09×10 6-7.26×10 6) copies/L and 0.99×10 6 (0.25×10 6-4.10×10 6) copies/L, respectively, which were significantly higher than that in the healthy control group[0.09×10 6 (0.01×10 6-0.35×10 6) copies/L]( H=33.34, 24.69; all P<0.01). Besides, the plasma ccf-mtDNA level in the PCD group was higher than that in the DCM group ( H=6.31, P<0.05). In the PCD group, the plasma ccf-mtDNA level was negatively correlated with the blood free carnitine level and left ventricular ejection fraction ( r=-0.85, -0.82, all P<0.05) and positively correlated with the modified Ross score and the N-terminal pro B type natriuretic peptide level ( r=0.81, 0.83, all P<0.05) before L-carnitine treatment.After treatment, the plasma ccf-mtDNA level decreased, and the blood free carnitine level and cardiac function recovered in the PCD group.The plasma ccf-mtDNA level declined sharply from the 3 rd month[0.96×10 6(0.50×10 6-2.27×10 6) copies/L] after treatment ( Z=2.24, P<0.05) and got to 0.27×10 6 (0.18×10 6-0.76×10 6) copies/L, 0.29×10 6(0.19×10 6-0.78×10 6) copies/L, and 0.16×10 6(0.10×10 6-1.06×10 6) copies/L at the 6 th, 9 th, and 12 th months after treatment, respectively, with no statistically significant difference compared to the healthy control group[0.09×10 6(0.01×10 6-0.35×10 6) copies/L] ( Z=1.23, 1.09, 2.12; all P>0.05). Conclusions:Plasma ccf-mtDNA may act as one pathogenic factor of cardiomyopathy in PCD, and monitoring its level is clinically important for heart condition assessment in PCD.