Document Detail


Mitochondrial DNA haplogroups influence AIDS progression.
MedLine Citation:
PMID:  19005266     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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 single-nucleotide 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.
Authors:
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
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Publication Detail:
Type:  Journal Article; Multicenter Study; Research Support, N.I.H., Extramural; Research Support, N.I.H., Intramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  AIDS (London, England)     Volume:  22     ISSN:  1473-5571     ISO Abbreviation:  AIDS     Publication Date:  2008 Nov 
Date Detail:
Created Date:  2008-11-13     Completed Date:  2009-02-20     Revised Date:  2013-06-04    
Medline Journal Info:
Nlm Unique ID:  8710219     Medline TA:  AIDS     Country:  England    
Other Details:
Languages:  eng     Pagination:  2429-39     Citation Subset:  IM; X    
Affiliation:
Laboratory of Genomic Diversity, National Cancer Institute, Frederick, Maryland 21702-1201, USA. hendricksons@mail.nih.gov
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MeSH Terms
Descriptor/Qualifier:
Adult
Antiretroviral Therapy, Highly Active
Cohort Studies
DNA, Mitochondrial / genetics*,  immunology
Disease Progression
Female
HIV Infections / genetics*,  immunology,  mortality
HIV-1 / genetics*,  immunology
Haplotypes / genetics*,  immunology
Humans
Male
Middle Aged
Polymorphism, Single Nucleotide
Grant Support
ID/Acronym/Agency:
1 R01 HD41224/HD/NICHD NIH HHS; 5-MO1-RR-00722/RR/NCRR NIH HHS; AG25638/AG/NIA NIH HHS; DK73691/DK/NIDDK NIH HHS; N01-CO-12400/CO/NCI NIH HHS; N02-CP-55504/CP/NCI NIH HHS; R01 AG24373/AG/NIA NIH HHS; UO1-AI-35039/AI/NIAID NIH HHS; UO1-AI-35040/AI/NIAID NIH HHS; UO1-AI-35041/AI/NIAID NIH HHS; UO1-AI-35042/AI/NIAID NIH HHS; UO1-AI-35043/AI/NIAID NIH HHS; UO1-AI-37613/AI/NIAID NIH HHS; UO1-AI-37984/AI/NIAID NIH HHS; Z99 CA999999/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/DNA, Mitochondrial
Comments/Corrections

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