Correlation between A3243G and G9053A mtDNA mutations and ATP levels in diabetes mellitus patients using qPCR and electrochemical aptasensors
Background and purpose: Mitochondrial DNA (mtDNA) mutations can impair oxidative phosphorylation and ATP production, potentially contributing to the pathogenesis of type 2 diabetes mellitus (T2DM). This study aimed to investigate the relationship between mtDNA mutations and ATP levels in blood and...
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| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
International Association of Physical Chemists (IAPC)
2025-06-01
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| Series: | ADMET and DMPK |
| Subjects: | |
| Online Access: | https://pub.iapchem.org/ojs/index.php/admet/article/view/2767 |
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| Summary: | Background and purpose: Mitochondrial DNA (mtDNA) mutations can impair oxidative phosphorylation and ATP production, potentially contributing to the pathogenesis of type 2 diabetes mellitus (T2DM). This study aimed to investigate the relationship between mtDNA mutations and ATP levels in blood and urine samples from T2DM patients. Experimental approach: Samples from 60 patients (30 with T2DM + mitochondrial disease [MD] phenotype and 30 with T2DM alone) were analyzed. mtDNA mutations A3243G and G9053A were detected using qPCR with dual-labeled probes (FAM for mutant, HEX for wild type) based on Cq comparisons. ATP concentrations were measured using a screen-printed carbon electrode (SPCE)-based electrochemical aptasensor. Key results: The A3243G mutation was more frequent and had higher heteroplasmy levels than G9053A, particularly in the T2DM + MD group. Although no statistically significant differences in ATP levels were observed between groups, descriptive ranges showed lower ATP concentrations in the T2DM + MD group (314 to 919 µM) compared to the T2DM group (746 to 1130 µM), both below the physiological range (1.500 to 1.900 µM). A similar pattern was found for A3243G mutation levels, while G9053A levels overlapped between groups. Two-way ANOVA showed a significant association between mutation presence and reduced ATP levels. Conclusion: The A3243G mutation may be more directly associated with mitochondrial ATP depletion in T2DM, while the role of G9053A remains inconclusive. This study highlights the potential of combining molecular and electrochemical tools to assess mitochondrial contributions in diabetes.
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| ISSN: | 1848-7718 |