Mitochondrial DNA population variation is not associated with Alzheimer's in the Japanese population: A consistent finding across global populations.

Autor: Wong J; The Bioscience Institute, Newcastle University, Newcastle upon Tyne, United Kingdom., Steyn JS; Research Software Engineering, Newcastle Helix, Newcastle upon Tyne, United Kingdom., Pienaar IS; Institute of Clinical Sciences, University of Birmingham, Edgbaston, United Kingdom., Elson JL; The Bioscience Institute, Newcastle University, Newcastle upon Tyne, United Kingdom.; The Centre for Human Metabolomics, North-West University, Potchefstroom, South Africa.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2022 Oct 20; Vol. 17 (10), pp. e0276169. Date of Electronic Publication: 2022 Oct 20 (Print Publication: 2022).
DOI: 10.1371/journal.pone.0276169
Abstrakt: Several mitochondrial DNA (mtDNA) haplogroup association studies have suggested that common mtDNA variants are associated with multifactorial diseases, including Alzheimer's disease (AD). However, such studies have also produced conflicting results. A new mtDNA association model, the 'variant load model' (VLM), has been applied to multiple disease phenotypes. Application of the VLM in a 2017 study failed to find different variant loads in AD patients compared to controls, in two cohorts of European origin. The study also suggested a lower variant load in healthy elderly individuals, but could offer no replicate cohort to support this observation. Here, the VLM is applied to Japanese mtDNA sequences; in doing so, we explored the role of mtDNA variation in AD and ageing in a different global population. Consistent with the previous findings using the VLM in two populations of European origin, we found no evidence for an association between rarer, non-haplogroup associated variation and the development of AD. However, the result in the context of ageing that suggested those with fewer mildly deleterious mutations might undergo healthier ageing, was not replicated. In contrast to our previous study, our present results suggest that those living to advanced old age may harbour more mildly deleterious mtDNA variations. Importantly our analysis showed this finding is not primarily being driven by many rare population variants dispersed across the mtDNA, but by a few more frequent variants with high MutPred scores. It is suggested the variants in question do not exert a mildly deleterious effect in their most frequent haplogroup context.
Competing Interests: The authors have declared that no competing interests exist.
Databáze: MEDLINE
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