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Genome-wide changes in subcutaneous adipose tissue expression in HIV negative adults after 2 weeks of zidovudine or stavudine with lamivudine.

ABSTRACT: As controversy remains as to the exact mechanisms by which the thymidine-analogue nucleoside reverse transcriptase inhibitors, zidovudine (AZT) and stavudine (d4T) induce subcutaneous adipose tissue toxicity, we used microarrays to dentify patterns of gene expression in human subcutaneous adipose tissue that change as a result of exposure to these drugs for 2 weeks.

ORGANISM(S): Homo sapiens

PROVIDER: GSE34302 | GEO | 2012/03/15

SECONDARY ACCESSION(S): PRJNA151523

REPOSITORIES: GEO

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Genome-wide changes in subcutaneous adipose tissue expression in HIV negative adults after 2 weeks of zidovudine or stavudine with lamivudine.

Project description:As controversy remains as to the exact mechanisms by which the thymidine-analogue nucleoside reverse transcriptase inhibitors, zidovudine (AZT) and stavudine (d4T) induce subcutaneous adipose tissue toxicity, we used microarrays to dentify patterns of gene expression in human subcutaneous adipose tissue that change as a result of exposure to these drugs for 2 weeks. Paired RNA samples (baseline and week 2), isolated from the adipose tissue of HIV-uninfected healthy adults randomized to 6 weeks of either AZT/ lamivudine (3TC) or d4T/ 3TC were analysed by microarray.

2012-03-15 | E-GEOD-34302 | biostudies-arrayexpress

Differential adipose tissue gene expression profiles in abacavir treated patients that may contribute to cardiovascular risk: a microarray study

Project description:Objective: to compare changes in gene expression by microarray from subcutaneous adipose tissue from HIV treatment naïve patients treated with efavirenz based regimens containing abacavir (ABC), tenofavir (TDF) or zidovidine (AZT). There were significant divergence between ABC and the other two groups 6 months after treatment in genes controlling cell adhesion and environmental information processin, with some convergence at 18 months. Compared to HIV negative controls the ABC group, but not AZT or TDF, showed enrichment of genes controlling adherence junction at six months and 184 months (adjusted p <0.05), and cell matrix adhesion (adjusted p<3.4E-0.5) at 6 months. Tight junction (p=0.03), gap junction (p<0.05) and leukocyte transendothelial migration (p=0.03) were over-expressed in ABC compared to TDF at 6 m. Enrichment pathways and individual genes controlling cell adhesion and environmental information processing were specifically dysregulated in the ABC group compared with the other treatments, There was little difference between AZT and TDF. Conclusion: After initiating treatment, there is divergence in the expression of genes controlling cell adhesion and environmental information processing between ABC and both TDF and AZT in subcutaneous adipose tissue. If similar changes are taking place in other tissues including the coronary vasculature, they may contribute to the observed increased risk of cardiovascular events reported in patients recently started on abacavir-containing regimens.

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