Mitochondrial DNA Haplogroups and Neurocognitive Impairment During HIV Infection.

TitleMitochondrial DNA Haplogroups and Neurocognitive Impairment During HIV Infection.
Publication TypeJournal Article
Year of Publication2015
AuthorsHulgan, T, Samuels, DC, Bush, W, Ellis, RJ, Letendre, SL, Heaton, RK, Franklin, DR, Straub, P, Murdock, DG, Clifford, DB, Collier, AC, Gelman, BB, Marra, CM, McArthur, JC, J McCutchan, A, Morgello, S, Simpson, DM, Grant, I, Kallianpur, AR
Corporate AuthorsCHARTER Group
JournalClin Infect Dis
Volume61
Issue9
Pagination1476-84
Date Published2015 Nov 1
ISSN1537-6591
Abstract

BACKGROUND: Neurocognitive impairment (NCI) remains an important complication in persons infected with human immunodeficiency virus (HIV). Ancestry-related mitochondrial DNA (mtDNA) haplogroups have been associated with outcomes of HIV infection and combination antiretroviral therapy (CART), and with neurodegenerative diseases. We hypothesize that mtDNA haplogroups are associated with NCI in HIV-infected adults and performed a genetic association study in the CNS HIV Antiretroviral Therapy Effects Research (CHARTER) cohort.

METHODS: CHARTER is an observational study of ambulatory HIV-infected adults. Haplogroups were assigned using mtDNA sequence, and principal components were derived from ancestry-informative nuclear DNA variants. Outcomes were cross-sectional global deficit score (GDS) as a continuous measure, GDS impairment (GDS ≥ 0.50), and HIV-associated neurocognitive disorder (HAND) using international criteria. Multivariable models were adjusted for comorbidity status (incidental vs contributing), current CART, plasma HIV RNA, reading ability, and CD4 cell nadir.

RESULTS: Haplogroups were available from 1027 persons; median age 43 years, median CD4 nadir 178 cells/mm(3), 72% on CART, and 46% with HAND. The 102 (9.9%) persons of genetically determined admixed Hispanic ancestry had more impairment by GDS or HAND than persons of European or African ancestry (P < .001 for all). In multivariate models including persons of admixed Hispanic ancestry, those with haplogroup B had lower GDS (β = -0.34; P = .008) and less GDS impairment (odds ratio = 0.16; 95% confidence interval, .04, .63; P = .009) than other haplogroups. There were no significant haplogroup associations among persons of European or African ancestry.

CONCLUSIONS: In these mostly CART-treated persons, mtDNA haplogroup B was associated with less NCI among persons of genetically determined Hispanic ancestry. mtDNA variation may represent an ancestry-specific factor influencing NCI in HIV-infected persons.

DOI10.1093/cid/civ527
Alternate JournalClin. Infect. Dis.
PubMed ID26129753
PubMed Central IDPMC4599391
Grant ListP30 MH062512 / MH / NIMH NIH HHS / United States