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- Title
Hemochromatosis Gene Polymorphisms, Mitochondrial Haplogroups, and Peripheral Lipoatrophy during Antiretroviral Therapy.
- Authors
Hulgan, Todd; Tebas, Pablo; Canter, Jeffrey A.; Mulligan, Kathleen; Haas, David W.; Dubé, Michael; Grinspoon, Steven; Robbins, Gregory K.; Motsinger, Alison A.; Kallianpur, Asha R.
- 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.
- Subjects
HEMOCHROMATOSIS; GENETIC polymorphisms; ANTIRETROVIRAL agents; NEUROPATHY; OXIDATIVE stress; LIGHT absorption; ANTIVIRAL agents; CLINICAL medicine; PREVENTIVE medicine; CLINICAL trials
- Publication
Journal of Infectious Diseases, 2008, Vol 197, Issue 6, p858
- ISSN
0022-1899
- Publication type
Article
- DOI
10.1086/528697