Browse by author
Lookup NU author(s): Dr Joanna Elson, Dr Jannetta Steyn
Full text for this publication is not currently held within this repository. Alternative links are provided below where available.
© 2023Background: Mitochondrial DNA (mtDNA) genetic variation is associated with neurocognitive (NC) impairment (NCI) in people with HIV (PWH). Other approaches use sequence conservation and protein structure to predict the impact of mtDNA variants on protein function. We examined predicted mtDNA variant pathogenicity in the CHARTER study using MutPred scores, hypothesizing that persons with higher scores (greater predicted pathogenicity) have more NCI. Methods: CHARTER included NC testing in PWH from 2003 to 2007. MutPred scores were assigned to CHARTER participants with mtDNA sequence; any score > 0.5 was considered potentially deleterious. Outcomes at cohort entry were NCI, defined by global and seven NC domain deficit scores, and by mean global and domain NC performance T-scores. Univariate and multivariable regression analyses assessed associations between having a deleterious variant and NCI. Additional models included estimated peripheral blood cell mtDNA copy number. Results: Data were available for 744 PWH (357 African ancestry; 317 European; 70 Hispanic). In the overall cohort, PWH having any potentially deleterious variant were less likely to have motor impairment (16 vs. 25 %, p = 0.001). In multivariable analysis, having a deleterious variant remained associated with lower likelihood of motor impairment (adjusted odds ratio 0.59 [95 % CI 0.41–0.88]; p = 0.009), and better motor performance by T-score (β 1.71 [0.31–3.10], p = 0.02). Associations persisted after adjustment for estimated mtDNA quantity. Conclusions: In these PWH, having a potentially deleterious mtDNA variant was associated with less motor impairment. These unexpected findings suggest that potentially deleterious mtDNA variations may confer protection against impaired motor function by as yet unknown mechanisms.
Author(s): Volpe KE, Samuels DC, Elson JL, Steyn JS, Gebretsadik T, Ellis RJ, Heaton RK, Kallianpur AR, Letendre S, Hulgan T
Publication type: Article
Publication status: Published
Journal: Mitochondrion
Year: 2024
Volume: 74
Print publication date: 01/01/2024
Online publication date: 19/11/2023
Acceptance date: 03/11/2023
ISSN (print): 1567-7249
ISSN (electronic): 1872-8278
Publisher: Elsevier B.V.
URL: https://doi.org/10.1016/j.mito.2023.11.003
DOI: 10.1016/j.mito.2023.11.003
PubMed id: 37989461
Altmetrics provided by Altmetric
