TY - JOUR
T1 - Mitochondrial DNA haplogroups influence AIDS progression
AU - Hendrickson, Sher L.
AU - Hutcheson, Holli B.
AU - Ruiz-Pesini, Eduardo
AU - Poole, Jason C.
AU - Lautenberger, James
AU - Sezgin, Efe
AU - Kingsley, Lawrence
AU - Goedert, James J.
AU - Vlahov, David
AU - Donfield, Sharyne
AU - Wallace, Douglas C.
AU - O'Brien, Stephen J.
PY - 2008
Y1 - 2008
N2 - 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.
AB - 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.
KW - AIDS
KW - Apoptosis
KW - Disease
KW - HIV-1
KW - Mitochondria
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U2 - 10.1097/QAD.0b013e32831940bb
DO - 10.1097/QAD.0b013e32831940bb
M3 - Article
C2 - 19005266
AN - SCOPUS:57349139384
SN - 0269-9370
VL - 22
SP - 2429
EP - 2439
JO - AIDS
JF - AIDS
IS - 18
ER -