Mitochondrial DNA mutations in complex I and tRNA genes in Parkinson’s disease

Abstract

mtDNA mutations with a high mutational burden (present in a high percentage of mtDNA molecules in an individual) in complex I or tRNA genes do not play a major role in the risk of PD in most PD patients. Further investigations are necessary to determine if any of the rare mtDNA mutations identified in PD patients play a role in the pathogenesis of PD in those few cases.

Does Mitochondrial DNA Play a Role in Parkinson's Disease? A Review of Cybrid and Other Supportive Evidence

“…In most cases, though, replication of such reported associations is inconsistent or awaits confirmation. For example, an A4336G transition in the mtDNA tRNA (Gln) gene has been found to be over-represented in PD subjects in some but not other studies (78,118,122,139). More recently, one large study found that a common nt10398G change is underrepresented in PD subjects, but a second study did not (123,151).…”

“…More recently, one large study found that a common nt10398G change is underrepresented in PD subjects, but a second study did not (123,151). A G5460A transition was found in one study to associate with PD, but this was not seen in other cohorts (62,122,139). The ND1 gene T4216C polymorphism has reportedly associated with an elevated risk of PD (60,107).…”

“…2). Most initial attempts to demonstrate a genetic basis for the PD complex I defect were sequence based and either negative or, if positive, not supported through replication (62,118,122,123,139). The first durable data to strongly make a case for mitochondrial DNA (mtDNA) as an important idiopathic PD mediator come not from sequence based studies, but rather from studies of cytoplasmic hybrids, or ''cybrids'' (130).…”

Mitochondrial proteomics as a selective tool for unraveling Parkinson’s disease pathogenesis

“…Moreover, as with toxin-evoked mtDNA damage, several reports contradict claims of inheritable defects in mtDNA. For example, investigators reported that no evidence was found of homoplasmic mtDNA single-nucleotide point-mutations in exons of DNA isolated from white blood cells [79] or in post-mortem SN samples taken from PD patients [80]. It is hoped that modern technologies, such as proteomics, will serve to elucidate on such controversial reports.…”

Complex I polymorphisms, bigenomic heterogeneity, and family history in Virginians with Parkinson's disease

“…Association studies of polymorphisms in several complex I genes or genes related to complex I subunit production suggest complex I variation might increase or decrease one's risk of developing PD [8][9][10][11][12][13][14][15]. However, positive association study results are counter-balanced by negative studies [14,[16][17][18][19][20]. The importance of complex I or complex Irelated gene polymorphisms in PD remains controversial.…”