The mitogenome mutation repertoire affects progression of Parkinson's Disease.

Abstract

Mitochondrial genome variation is a risk factor for Parkinson's disease, but its role in levodopa-induced dyskinesia remains incompletely understood. This study examines the mitochondrial mutation repertoire as a potential biomarker for levodopa-induced dyskinesia in patients with Parkinson's disease. We analyzed the mitogenome using next-generation sequencing data from 42 controls and 45 people with Parkinson's (25 without dyskinesia and 20 with dyskinesia). The mtDNA-server 2 workflow was applied for variant calling analysis. Transition and transversion rates vary during disease progression, especially in patients without levodopa-induced dyskinesia. Although the occurrence of these mutations does not follow a linear pattern, the frequency of transitions modestly increases with age. Specific coding regions (CO1, CO2, CO3, ND4, ND5, and ND6) and the regulatory region (RNR2) exhibited an enrichment of transitions and transversions in patients without dyskinesia. Additionally, we have upgraded the mtDNA-network tool (https://apps.lghm.ufpa.br/mtdna) with an integrated visual component that summarizes the mitochondrial profile in Parkinson's disease. The study highlights dynamic shifts in the mitochondrial mutation repertoire, with clinical implications for underrepresented populations, underscoring the importance of accounting for genetic characteristics across diverse groups.