title: Methodological considerations in human studies of gene expression in HIV-associated lipodystrophy.
abstract: In the majority of cases, HIV-associated lipodystrophy, lipoatrophy in particular, becomes clinically apparent only after months or years of continuous exposure to antiretroviral medications and, once developed, is difficult to reverse. Many lipid-related side effects of antiretroviral medications result from drug-induced changes in gene expression. As our understanding of the pathogenic mechanisms underlying HIV-associated lipodystrophy improves, it is important to be able to explore changes at a molecular level in order to fully elucidate the mechanisms whereby antiretroviral drugs exert their toxicities. Monitoring changes in gene expression in vivo may enable physicians to identify, predict or prevent drug toxicities early, before irreversible changes in body composition occur. However, monitoring changes in gene expression at a population level presents many methodological challenges that need to be addressed, over and above the considerable intra- and inter-individual variability inherent in the cellular expression of any gene. Careful collection and processing of adequate biological samples, robust laboratory processes and assays, and appropriate study design can help overcome many of these difficulties.
authors.affiliation: National Centre in HIV Epidemiology and Clinical Research, University of New South Wales, Sydney, Australia. p.mallon@cfi.unsw.edu.au
authors.forename: Patrick W G
authors.initials: PW
authors.lastname: Mallon
authors.forename: Rebecca
authors.initials: R
authors.lastname: Sedwell
authors.forename: Patrick
authors.initials: P
authors.lastname: Unemori
authors.forename: Anthony
authors.initials: A
authors.lastname: Kelleher
authors.forename: David A
authors.initials: DA
authors.lastname: Cooper
authors.forename: Andrew
authors.initials: A
authors.lastname: Carr
mesh_terms: D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics; D018076:DNA, Complementary / Q000032:analysis; D004268:DNA-Binding Proteins / Q000235:genetics; D015870:Gene Expression; D039682:HIV-Associated Lipodystrophy Syndrome / Q000378:metabolism*; D006801:Humans; D016133:Polymerase Chain Reaction; D012313:RNA / Q000032:analysis / Q000302:isolation & purification; D012107:Research Design; D013048:Specimen Handling; D051780:Sterol Regulatory Element Binding Protein 1; D014157:Transcription Factors / Q000235:genetics
chemical_list: D022762:CCAAT-Enhancer-Binding Proteins; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; C497387:SREBF1 protein, human; D051780:Sterol Regulatory Element Binding Protein 1; D014157:Transcription Factors; D012313:RNA