Mitochondrial DNA A4336G Mutation in Alzheimer’s and Parkinson’s Diseases

Abstract

Objectives: To determine whether the mitochondrial DNA (mtDNA) A4336G mutation represents a risk factor for Spanish patients with both Alzheimer’s disease (AD) and Parkinson’s disease (PD). Material and Methods: One hundred and sixty-one AD and 106 PD unrelated patients were included in the study. Seventy-eight age-matched and 144 randomly chosen healthy subjects served as controls. The frequency of the A4336G mutation in these groups was compared using the χ² and Fisher’s exact tests. p < 0.05 was established as a statistically significant differential value. Results: The mtDNA A4336G mutation was present in 1/161 of AD patients (0.6%), in 3/106 of PD patients (2.8%), in 1/78 of age-matched controls (1.3%) and in 2/144 of the randomly chosen controls (1.4%). These differences were not statistically significant. Conclusion: Our results do not support the hypothesis that this mutation represents a risk factor for either AD or PD patients, at least in the case of this Spanish sample.

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

“…Prior studies of tRNA Gln 4336C in PD reported either positive or absent associations [8,9,16,17,19,20].None found, as we did, an over-representation of tRNA Gln 4336C in control subjects. While particular mtDNA signatures may reduce PD risk [15], the rarity of tRNA Gln 4336C in our study precludes us from postulating this polymorphism protects against PD in some populations.…”

“…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.…”

“…This is a synthetic gene required for translation of mtDNA-encoded ETC structural genes, and therefore can be considered a complex I-relevant gene. Negative association studies for each of these polymorphisms in PD also exist [16][17][18][19][20]. Because of our interest in how complex I dysfunction arises in and may contribute to PD, we attempted to replicate studies reporting a positive association between PD and complex I subunit or complex I-related gene polymorphisms.…”

Mitochondrial DNA mutations in neurodegeneration

“…In parallel, a separate study also showed an age associated with around 5% of AD cases and only extremely rarely in controls 594 [122,123], this finding has not been replicated in all cohorts [124,125]. The association between ischemic stroke and mitochondrial 627 haplogroups has also been contentious due to the majority of studies 628 having been conducted in small, discrete and differing ethnic cohorts.…”

Association of mitochondrial variants A4336G of the tRNAGln gene and 8701G/A of the MT-ATP6 gene in Mexicans Mestizos with Parkinson disease

“…Additionally, a study in the Spanish population found an association between the tRNAGln 4336 mitochondrial DNA variant and PD [25]. However, other studies did not corroborate this association in different populations [1,9,23,35].…”