Mitochondrial Variants of Complex I Genes as Potential Biomarkers to Leprosy

Abstract

Abstract Background: Leprosy is a chronic bacterial infection mainly caused by Mycobacterium leprae that primarily affects skin and peripheral nerves. Due to its ability to absorb carbon from the host cell, the bacillus became dependent on energy production, mainly through oxidative phosphorylation. In fact, variations in genes of Complex I of oxidative phosphorylation encoded by mtDNA have been associated with several diseases in humans, including bacterial infections, which are possible influencers in the host response to leprosy. Here, we investigated the presence of variants in the mtDNA genes encoding Complex I regarding leprosy, as well as the analysis of their pathogenicity in the studied cohort. Results: We found a sum of 74 variants exclusive of only one leprosy pole (Pole T: Borderline Tuberculoid; Pole L: Borderline Lepromatous and Lepromatous), suggesting a possible clinical significance to these variants. Notably, six variants were exclusively found in both clinical poles of leprosy, including m.4158A>G and m.4248T>C in MT-ND1, m.13650C>A, m.13674T>C, m.12705C>T and m.13263A>G in MT-ND5, of which there are no previous reports in the global literature. Conclusions: Our observations reveal a substantial number of mutations among different groups of leprosy, highlighting a diverse range of genomic consequences associated with mutations in genes across these groups. Furthermore, we suggest that the four specific variants exclusively identified in the case group could potentially play a crucial role in leprosy susceptibility and its clinical differentiation. These variants are believed to contribute to the instability and dysregulation of oxidative phosphorylation during the infection, further emphasizing their significance.