Genetic analysis implicates resistin in HIV lipodystrophy.
OBJECTIVE
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).


CONCLUSIONS
Genetic variation in resistin is associated with metabolic complications caused by HAART.
Ranade
Koustubh
K
Bristol-Myers Squibb R&D, Princeton, New Jersey 08543-5400, USA. koustubh.ranade@bms.com
Geese
William J
WJ
Noor
Mustafa
M
Flint
Oliver
O
Tebas
Pablo
P
Mulligan
Kathleen
K
Powderly
William
W
Grinspoon
Steven K
SK
Dube
Michael P
MP
D000328:Adult; D044966:Anti-Retroviral Agents / Q000009:adverse effects* / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects; D001786:Blood Glucose / Q000032:analysis; D001823:Body Composition / Q000187:drug effects; D002784:Cholesterol / Q000097:blood; D016000:Cluster Analysis; D005838:Genotype; D039682:HIV-Associated Lipodystrophy Syndrome / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D052243:Resistin / Q000235:genetics* / Q000378:metabolism; D018570:Risk Assessment / Q000379:methods; D017421:Sequence Analysis; D014280:Triglycerides / Q000097:blood
D044966:Anti-Retroviral Agents; D001786:Blood Glucose; D052243:Resistin; D014280:Triglycerides; D002784:Cholesterol