Genetic analysis implicates resistin in HIV lipodystrophy

AIDS. 2008 Aug 20;22(13):1561-8. doi: 10.1097/QAD.0b013e32830a9886.


Objectives: To investigate the role of genetic variation in influencing the risk of metabolic complications associated with highly active antiretroviral therapy (HAART).

Methods: Cluster analysis of metabolic traits of 189 patients enrolled in ACTG5005s, the metabolic substudy of ACTG384, a clinical trial of HAART, was performed to identify a subgroup of individuals with increased risk of developing a cluster of metabolic abnormalities after exposure to HAART. Almost 300 single nucleotide polymorphisms in 135 candidate genes were evaluated for their association with this subgroup.

Results: A subgroup of patients was identified that had a normal metabolic profile at baseline but developed significantly elevated lipids and insulin resistance on HAART. This high-risk subgroup of patients also experienced significant body composition changes, particularly limb fat loss. Candidate gene analysis revealed that a single nucleotide polymorphism in resistin, a gene previously implicated in obesity and insulin resistance, was associated with this high-risk group (P = 0.0003).

Conclusion: Genetic variation in resistin is associated with metabolic complications caused by HAART.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-Retroviral Agents / adverse effects*
  • Anti-Retroviral Agents / therapeutic use
  • Antiretroviral Therapy, Highly Active / adverse effects
  • Blood Glucose / analysis
  • Body Composition / drug effects
  • Cholesterol / blood
  • Cluster Analysis
  • Genotype
  • HIV-Associated Lipodystrophy Syndrome / drug therapy
  • HIV-Associated Lipodystrophy Syndrome / genetics*
  • HIV-Associated Lipodystrophy Syndrome / metabolism
  • Humans
  • Insulin Resistance
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide*
  • Resistin / genetics*
  • Resistin / metabolism
  • Risk Assessment / methods
  • Sequence Analysis
  • Triglycerides / blood


  • Anti-Retroviral Agents
  • Blood Glucose
  • Resistin
  • Triglycerides
  • Cholesterol