Mitochondrial DNA haplogroups influence AIDS progression

Sher L. Hendrickson, Holli B. Hutcheson, Eduardo Ruiz-Pesini, Jason C. Poole, James Lautenberger, Efe Sezgin, Lawrence Kingsley, James J. Goedert, David Vlahov, Sharyne Donfield, Douglas C. Wallace, Stephen J. O'Brien

Research output: Contribution to journalArticlepeer-review

Abstract

Objective: Mitochondrial function plays a role in both AIDS progression and HAART toxicity; therefore, we sought to determine whether mitochondrial DNA variation revealed novel AIDS restriction genes, particularly as mitochondrial DNA singlenucleotide polymorphisms are known to influence regulation of oxidative phosphorylation, reactive oxygen species production, and apoptosis. Design: This is a retrospective cohort study. Methods: We performed an association study of mitochondrial DNA haplogroups among 1833 European American HIV-1 patients from five US cohorts: the Multicenter AIDS Cohort Study, the San Francisco City Clinic Study, Hemophilia Growth and Development Study, the Multicenter Hemophilia Cohort Study, and the AIDS Linked to Intravenous Experiences cohort to determine whether the mitochondrial DNA haplogroup correlated with AIDS progression rate. Results: Mitochondrial DNA haplogroups J and U5a were elevated among HIV-1 infected people who display accelerated progression to AIDS and death. Haplogroups Uk, H3, and IWX appeared to be highly protective against AIDS progression. Conclusion: The associations found in our study appear to support a functional explanation by which mitochondrial DNA variation among haplogroups, influencing ATP production, reactive oxygen species generation, and apoptosis, is correlated to AIDS disease progression; however, repeating these results in cohorts with different ethnic backgrounds would be informative. These data suggest that mitochondrial genes are important indicators of AIDS disease progression in HIV-1 infected persons.

Original languageEnglish (US)
Pages (from-to)2429-2439
Number of pages11
JournalAIDS
Volume22
Issue number18
DOIs
StatePublished - 2008
Externally publishedYes

Keywords

  • AIDS
  • Apoptosis
  • Disease
  • HIV-1
  • Mitochondria

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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