Key result
Seven possible pathogenic mt-tRNA mutations were identified in patients with dilated cardiomyopathy but were absent in controls, suggesting they may cause mitochondrial dysfunction responsible for DCM.
Why the study?
Dilated cardiomyopathy has an unknown etiology and mitochondrial dysfunction is believed to be involved, prompting evaluation of the association between mitochondrial tRNA mutations and the disease.
Are mitochondrial tRNA mutations associated with dilated cardiomyopathy?
Case-Control (n=518)
Are mitochondrial tRNA mutations associated with dilated cardiomyopathy?
Mitochondrial tRNA mutations may contribute to the pathogenesis of dilated cardiomyopathy by causing mitochondrial dysfunction.
mt-tRNA mutations were associated with DCM and mitochondrial dysfunction; leaves open causal contribution and need for replication before clinical consideration.
OBJECTIVES: Dilated cardiomyopathy (DCM) is a complex cardiovascular disease with unknown etiology. Although nuclear genes play active roles in DCM, mitochondrial dysfunction was believed to be involved in the pathogenesis of DCM. The objective of this study was to analyze the association between mitochondrial tRNA (mt-tRNA) mutations and DCM. MATERIALS AND METHODS: We performed a mutational analysis of mt-tRNA genes in a cohort of 318 patients with DCM and 200 age- and gender-matched control subjects. To further assess their pathogenicity, phylogenetic analysis and mitochondrial functions including mtDNA copy number, ATP, and ROS were analyzed. RESULTS: Seven possible pathogenic mutations, i.e., MT-TL1 3302A>G, MT-TI 4295A>G, MT-TM 4435A>G, MT-TA 5655T>C, MT-TH 12201T>C, MT-TE 14692A>G, and MT-TT 15927G>A, were identified in the DCM group but were absent in controls. These mutations occurred at extremely conserved nucleotides of corresponding tRNAs and led to the failure in tRNAs metabolism. Moreover, a significant reduction in ATP and mtDNA copy number and a marked increase in ROS level were observed in polymononuclear leukocytes (PMNs) derived from the DCM patients carrying these mt-tRNA mutations, suggesting that these mutations may cause mitochondrial dysfunction that was responsible for DCM. CONCLUSIONS: Our data indicated that mt-tRNA mutations may be the molecular basis for DCM, which provides novel insights into the pathophysiology of DCM that manifested as mitochondrial dysfunction.
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Qi et al. (2022) conducted a case-control in Dilated cardiomyopathy (n=518). Mitochondrial tRNA (mt-tRNA) mutations vs. Age- and gender-matched control subjects was evaluated on Presence of mt-tRNA mutations. Seven possible pathogenic mt-tRNA mutations were identified in patients with dilated cardiomyopathy but were absent in controls, suggesting they may cause mitochondrial dysfunction responsible for DCM.
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