Peripheral Blood Mitochondrial DNA Copy Number Obtained From Genome-Wide Genotype Data Is Associated With Neurocognitive Impairment in Persons With Chronic HIV Infection.
Title | Peripheral Blood Mitochondrial DNA Copy Number Obtained From Genome-Wide Genotype Data Is Associated With Neurocognitive Impairment in Persons With Chronic HIV Infection. |
Publication Type | Journal Article |
Year of Publication | 2019 |
Authors | Hulgan, T, Kallianpur, AR, Guo, Y, Barnholtz-Sloan, JS, Gittleman, H, Brown, TT, Ellis, R, Letendre, S, Heaton, RK, Samuels, DC |
Corporate Authors | CHARTER Study |
Journal | J Acquir Immune Defic Syndr |
Volume | 80 |
Issue | 4 |
Pagination | e95-e102 |
Date Published | 2019 04 01 |
ISSN | 1944-7884 |
Keywords | Adult, AIDS Dementia Complex, Anti-Retroviral Agents, DNA Copy Number Variations, DNA, Mitochondrial, Female, Genome-Wide Association Study, Genotype, HIV Infections, Humans, Male, Middle Aged, Mitochondria, neurocognitive disorders, Neuropsychological Tests |
Abstract | BACKGROUND: Mitochondrial DNA (mtDNA) copy number varies by cell type and energy demands. Blood mtDNA copy number has been associated with neurocognitive function in persons without HIV. Low mtDNA copy number may indicate disordered mtDNA replication; high copy number may reflect a response to mitochondrial dysfunction. We hypothesized that blood mtDNA copy number estimated from genome-wide genotyping data is related to neurocognitive impairment (NCI) in persons with HIV.METHODS: In the CNS HIV Antiretroviral Therapy Effects Research (CHARTER) study, peripheral blood mtDNA copy number was obtained from genome-wide genotyping data as a ratio of mtDNA single-nucleotide polymorphism probe intensities relative to nuclear DNA single-nucleotide polymorphisms. In a multivariable regression model, associations between mtDNA copy number and demographics, blood cell counts, and HIV disease and treatment characteristics were tested. Associations of mtDNA copy number with the global deficit score (GDS), GDS-defined NCI (GDS ≥ 0.5), and HIV-associated neurocognitive disorder (HAND) diagnosis were tested by logistic regression, adjusting for potential confounders.RESULTS: Among 1010 CHARTER participants, lower mtDNA copy number was associated with longer antiretroviral therapy duration (P < 0.001), but not with d-drug exposure (P = 0.85). mtDNA copy number was also associated with GDS (P = 0.007), GDS-defined NCI (P < 0.001), and HAND (P = 0.002). In all analyses, higher mtDNA copy number was associated with poorer cognitive performance.CONCLUSIONS: Higher mtDNA copy number estimated from peripheral blood genotyping was associated with worse neurocognitive performance in adults with HIV. These results suggest a connection between peripheral blood mtDNA and NCI, and may represent increased mtDNA replication in response to mitochondrial dysfunction. |
DOI | 10.1097/QAI.0000000000001930 |
Alternate Journal | J Acquir Immune Defic Syndr |
PubMed ID | 30531306 |
PubMed Central ID | PMC6391216 |
Grant List | K24 MH097673 / MH / NIMH NIH HHS / United States HHSN271201000030C / MH / NIMH NIH HHS / United States HHSN271201000036C / MH / NIMH NIH HHS / United States N01 MH022005 / MH / NIMH NIH HHS / United States P30 MH062512 / MH / NIMH NIH HHS / United States N01 MH022005 / MH / NIMH NIH HHS / United States R01 MH107345 / MH / NIMH NIH HHS / United States R01 MH095621 / MH / NIMH NIH HHS / United States |