LMNA messenger RNA expression in highly active antiretroviral therapy-treated HIV-positive patients

J Acquir Immune Defic Syndr. 2007 Dec 1;46(4):384-9. doi: 10.1097/qai.0b013e31815aba1b.

Abstract

The LMNA gene encodes for lamins A and C as major products, which are involved in nuclear stability, chromatin structure, and gene expression. Several LMNA mutations cause an insulin-resistant lipodystrophy that shares features with HIV-related lipodystrophy. Some HIV-treatment agents alter lamin A/C maturation, organization, and stability in 3T3-L1. We aimed to test the hypothesis that human adipose tissue LMNA expression can be altered in highly active antiretroviral therapy (HAART)-treated HIV-positive patients with lipodystrophy. We have also analyzed both isoforms and explored if their expression is associated with insulin resistance or inflammation in these patients. A cross-sectional study that analyzed abdominal subcutaneous adipose tissue from 39 treated HIV-positive patients (25 of whom had lipodystrophy) and 21 uninfected control subjects was performed. We have observed lower levels of lamin A isoform but normal levels of lamin C isoform in all HIV-infected patients, irrespective of the presence or absence of lipodystrophy, which reinforces the idea that an altered lamin A/C ratio could reflect a pathogenic condition. We have also found a correlation between LMNA adipose expression and several cytokine and adipogenic gene markers in HIV-positive patients, regardless of the presence or absence of lipodystrophy. Hence, in the present study, the lower lamin A expression observed in HIV-positive patients is related to HIV itself or to treatments rather than to the presence of lipodystrophy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / anatomy & histology*
  • Adipose Tissue / diagnostic imaging
  • Adult
  • Anthropometry
  • Antiretroviral Therapy, Highly Active*
  • CD4 Lymphocyte Count
  • Case-Control Studies
  • Cross-Sectional Studies
  • Cytokines / blood
  • Female
  • HIV Seropositivity / drug therapy*
  • Humans
  • Lamin Type A / genetics*
  • Male
  • Middle Aged
  • RNA, Messenger / genetics*
  • Reference Values
  • Regression Analysis
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tomography, X-Ray Computed
  • Viscera

Substances

  • Cytokines
  • LMNA protein, human
  • Lamin Type A
  • RNA, Messenger