European Mitochondrial DNA Haplogroups are Associated with Cerebrospinal Fluid Biomarkers of Inflammation in HIV Infection.

TitleEuropean Mitochondrial DNA Haplogroups are Associated with Cerebrospinal Fluid Biomarkers of Inflammation in HIV Infection.
Publication TypeJournal Article
Year of Publication2016
AuthorsSamuels, DC, Kallianpur, AR, Ellis, RJ, Bush, WS, Letendre, S, Franklin, D, Grant, I, Hulgan, T
JournalPathog Immun
Volume1
Issue2
Pagination330-351
Date Published2016 Fall-Winter
ISSN2469-2964
KeywordsCHARTER, Internal
Abstract

BACKGROUND: Mitochondrial DNA (mtDNA) haplogroups are ancestry-related patterns of single-nucleotide polymorphisms that are associated with differential mitochondrial function in model systems, neurodegenerative diseases in HIV-negative populations, and chronic complications of HIV infection, including neurocognitive impairment. We hypothesized that mtDNA haplogroups are associated with neuroinflammation in HIV-infected adults.METHODS: CNS HIV Antiretroviral Therapy Effects Research (CHARTER) is a US-based observational study of HIV-infected adults who underwent standardized neurocognitive assessments. Participants who consented to DNA collection underwent whole blood mtDNA sequencing, and a subset also underwent lumbar puncture. IL-6, IL-8, TNF-α (high-sensitivity), and IP-10 were measured in cerebrospinal fluid (CSF) by immunoassay. Multivariable regression of mtDNA haplogroups and log-transformed CSF biomarkers were stratified by genetic ancestry using whole-genome nuclear DNA genotyping (European [EA], African [AA], or Hispanic ancestry [HA]), and adjusted for age, sex, antiretroviral therapy (ART), detectable CSF HIV RNA, and CD4 nadir. A total of 384 participants had both CSF cytokine measures and genetic data (45% EA, 44% AA, 11% HA, 22% female, median age 43 years, 74% on ART).RESULTS: In analyses stratified by the 3 continental ancestry groups, no haplogroups were significantly associated with the 4 biomarkers. In the subgroup of participants with undetectable plasma HIV RNA on ART, European haplogroup H participants had significantly lower CSF TNF-α ( = 0.001).CONCLUSIONS: Lower CSF TNF-α may indicate lower neuroinflammation in the haplogroup H participants with well-controlled HIV on ART.

DOI10.20411/pai.v1i2.156
Alternate JournalPathog Immun
PubMed ID28317034
PubMed Central IDPMC5351881
Grant ListP30 MH062512 / MH / NIMH NIH HHS / United States
R01 MH095621 / MH / NIMH NIH HHS / United States
R01 MH107345 / MH / NIMH NIH HHS / United States