November 14, 2008

mtDNA haplogroups and AIDS progression

Another piece of evidence in favor of the claim that mtDNA variation may have been shaped by natural selection.

AIDS. 2008 Nov 30;22(18):2429-2439.

Mitochondrial DNA haplogroups influence AIDS progression.

Hendrickson SL, Hutcheson HB, Ruiz-Pesini E, Poole JC, Lautenberger J, Sezgin E, Kingsley L, Goedert JJ, Vlahov D, Donfield S, Wallace DC, Oʼbrien SJ.

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.



Maju said...


Considering that (if we except the poorly defined "IXW" clade) the mentioned haplogroups represent specially some geographically defined populations, it could just mean that Western/SW Europeans have overall better genetic protection against HIV-1 than Eastern Europeans and Eastern Mediterraneans. The decissive genes might well not be related to mtDNA as such, right?

Unknown said...

While I have no idea what the mtDNA haplogroups of my dead friends and acquaintances was, mine is H6a1a. Though at first (due to co-infection with EBV) my acute stage looked bad (as though I had had it for years, not months), I stabilised quickly, and with the newer meds, I've been doing decently for about 16 or 17 years, with several health issues in-between, but I am still alive. I do have horrible fatigue, though, and my mt group (at least the H group broadly) has been found by a study to be among the risk factors for lipodystrophy/lipoatrophy. The prior gave my neck and upper back weird fat accumulations, while stripping the fat from my extremities. But at least I am here, while so many friends are gone. I miss them.