title: Hemochromatosis gene polymorphisms, mitochondrial haplogroups, and peripheral lipoatrophy during antiretroviral therapy.
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.
authors.affiliation: Division of Infectious Diseases, Vanderbilt University School of Medicine, Nashville, Tennessee 37203, USA. todd.hulgan@vanderbilt.edu
authors.forename: Todd
authors.initials: T
authors.lastname: Hulgan
authors.forename: Pablo
authors.initials: P
authors.lastname: Tebas
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Canter
authors.forename: Kathleen
authors.initials: K
authors.lastname: Mulligan
authors.forename: David W
authors.initials: DW
authors.lastname: Haas
authors.forename: Michael
authors.initials: M
authors.lastname: Dubé
authors.forename: Steven
authors.initials: S
authors.lastname: Grinspoon
authors.forename: Gregory K
authors.initials: GK
authors.lastname: Robbins
authors.forename: Alison A
authors.initials: AA
authors.lastname: Motsinger
authors.forename: Asha R
authors.initials: AR
authors.lastname: Kallianpur
mesh_terms: D015502:Absorptiometry, Photon; D000328:Adult; D044966:Anti-Retroviral Agents / Q000009:adverse effects* / Q000627:therapeutic use; D004272:DNA, Mitochondrial / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy / Q000235:genetics* / Q000821:virology; D015497:HIV-1 / Q000302:isolation & purification*; D039682:HIV-Associated Lipodystrophy Syndrome / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism / Q000821:virology; D006432:Hemochromatosis / Q000235:genetics* / Q000378:metabolism / Q000821:virology; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide
chemical_list: D044966:Anti-Retroviral Agents; D004272:DNA, Mitochondrial