Genetic analysis implicates resistin in HIV lipodystrophy.

TitleGenetic analysis implicates resistin in HIV lipodystrophy.
Publication TypeJournal Article
Year of Publication2008
AuthorsRanade K, Geese WJ, Noor M, Flint O, Tebas P, Mulligan K, Powderly W, Grinspoon SK, Dubé MP
Date Published2008 Aug 20
KeywordsAdult, Anti-Retroviral Agents, Antiretroviral Therapy, Highly Active, Blood Glucose, Body Composition, Cholesterol, Cluster Analysis, Genotype, HIV-Associated Lipodystrophy Syndrome, Humans, Insulin Resistance, Male, Middle Aged, Polymorphism, Single Nucleotide, Resistin, Risk Assessment, Sequence Analysis, Triglycerides

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.

Alternate JournalAIDS
PubMed ID18670214
PubMed Central IDPMC4410015
Grant ListAI068636 / AI / NIAID NIH HHS / United States
AI38558 / AI / NIAID NIH HHS / United States
U01 AI038858 / AI / NIAID NIH HHS / United States
U01 AI068636 / AI / NIAID NIH HHS / United States