Hemochromatosis gene polymorphisms, mitochondrial haplogroups, and peripheral lipoatrophy during antiretroviral therapy.

TitleHemochromatosis gene polymorphisms, mitochondrial haplogroups, and peripheral lipoatrophy during antiretroviral therapy.
Publication TypeJournal Article
Year of Publication2008
AuthorsHulgan T, Tebas P, Canter JA, Mulligan K, Haas DW, Dubé M, Grinspoon S, Robbins GK, Motsinger AA, Kallianpur AR
Corporate AuthorsAIDS Clinical Trials Group 384 and A5005s Study Teams
JournalJ Infect Dis
Volume197
Issue6
Pagination858-66
Date Published2008 Mar 15
ISSN0022-1899
KeywordsAbsorptiometry, Photon, Adult, Anti-Retroviral Agents, DNA, Mitochondrial, Female, Genotype, Hemochromatosis, HIV Infections, HIV-1, HIV-Associated Lipodystrophy Syndrome, Humans, Male, Middle Aged, Polymorphism, Single Nucleotide
Abstract

BACKGROUND: Antiretroviral therapy (ART)-associated lipoatrophy involves mitochondrial dysfunction. Iron metabolism impacts mitochondrial function and oxidative stress. Mitochondrial haplogroups and hemochromatosis gene (HFE) polymorphisms have been associated with ART-induced neuropathy. We assessed relationships between these variants and lipoatrophy.

METHODS: The AIDS Clinical Trials Group 384 study randomized ART-naive individuals to receive didanosine-stavudine or zidovudine-lamivudine, combined with efavirenz and/or nelfinavir. Substudy A5005s evaluated fat distribution by dual-energy X-ray absorptiometry (DEXA). We characterized HFE polymorphisms 845G>A and 187C>G and European mitochondrial haplogroups in A5005s participants who consented to genetic analyses.

RESULTS: Among 96 participants (58% were white, and 10% were female) with baseline and 48 or 64 week DEXA data, the median limb fat change was -8.8% (interquartile range, -28.7% to +15.6%). HFE 187C/G heterozygotes (n = 23) had less limb fat loss than 187C/C homozygotes (n = 71) (+6.1% vs. -12.5%; P = .02) and were less likely to develop lipoatrophy after adjustment for age, sex, race, and ART randomization (odds ratio, 0.31; 95% confidence interval, 0.10-0.95; P = .04). Among non-Hispanic white participants, median limb fat change was +26.1% among 5 participants with mitochondrial haplogroup J, compared with -9.7% among 49 participants with other mitochondrial haplogroups (P = .07).

CONCLUSIONS: HFE 187C>G and, possibly, mitochondrial haplogroup J gave relative protection against lipoatrophy during ART in A5005s. These associations should be replicated in other studies.

DOI10.1086/528697
Alternate JournalJ. Infect. Dis.
PubMed ID18419350
Grant ListAI38858 / AI / NIAID NIH HHS / United States
AI46339 / AI / NIAID NIH HHS / United States
AI54999 / AI / NIAID NIH HHS / United States
AT002508 / AT / NCCIH NIH HHS / United States
U01 AI068636 / AI / NIAID NIH HHS / United States