Mitochondrial DNA haplogroups influence AIDS progression.
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.


METHODS
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.


CONCLUSIONS
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.
Hendrickson
Sher L
SL
Laboratory of Genomic Diversity, National Cancer Institute, Frederick, Maryland 21702-1201, USA. hendricksons@mail.nih.gov
Hutcheson
Holli B
HB
Ruiz-Pesini
Eduardo
E
Poole
Jason C
JC
Lautenberger
James
J
Sezgin
Efe
E
Kingsley
Lawrence
L
Goedert
James J
JJ
Vlahov
David
D
Donfield
Sharyne
S
Wallace
Douglas C
DC
O'Brien
Stephen J
SJ
D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D015331:Cohort Studies; D004272:DNA, Mitochondrial / Q000235:genetics* / Q000276:immunology; D018450:Disease Progression; D005260:Female; D015658:HIV Infections / Q000235:genetics* / Q000276:immunology / Q000401:mortality; D015497:HIV-1 / Q000235:genetics* / Q000276:immunology; D006239:Haplotypes / Q000235:genetics* / Q000276:immunology; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide
D004272:DNA, Mitochondrial