title: Contribution of genetic background and antiretroviral therapy to body fat changes in antiretroviral-naive HIV-infected adults.
abstract: OBJECTIVE
  To evaluate the association of host genetics with changes in limb or trunk fat in a group of antiretroviral therapy (ART)-naive HIV-infected patients prospectively followed up according to the initiation and the type of ART.
  
  
  METHODS
  Fifty single nucleotide polymorphisms (SNPs) in 26 genes, associated with obesity, insulin resistance, lipid metabolism or lipodystrophy in previously published genetic studies, were assessed in ART-naive HIV-infected Caucasian patients divided into three groups: 24 (27%) did not start ART, 29 (32.6%) received zidovudine or stavudine and 36 (40.4%) received neither zidovudine nor stavudine in their initial regimen. Patients underwent body fat measurements (using dual-energy X-ray absorptiometry) at baseline and Month 12. A multivariate model using backward stepwise elimination was used to assess the influence of SNPs and baseline levels of non-genetic covariates on changes in limb or trunk fat.
  
  
  RESULTS
  The baseline characteristics were: 73% men, 17% coinfected with hepatitis C virus and/or hepatitis B virus, median age 37 years, median CD4+ T cell count 228/mm(3), median HIV-RNA 5.2 log copies/mL, median plasma glucose 85 mg/dL, median plasma insulin 9.1 IU/mL, median limb fat 5.6 kg and median trunk fat 7.0 kg. There were no baseline differences among the three groups except for the CD4+ T cell count. The decrease in limb fat was greater in the no-ART group relative to the other two groups (P < 0.05). The multivariate model showed associations of rs1801278 in IRS1 (P = 0.029, OR = 0.13), baseline viral load (P = 0.006; OR = 4.453) and baseline glucose levels (P = 0.008, OR = 0.926) with loss of limb fat, and rs2228671 in LDLR (P = 0.012, OR = 0.108), rs405509 in APOE (P = 0.048, OR = 0.205), baseline viral load (P = 0.005, OR = 0.186) and baseline CD4+ T cell count (P = 0.01, OR = 1.008) with gain of trunk fat.
  
  
  CONCLUSIONS
  Specific polymorphisms in IRS1 (limb fat loss) and LDLR and APOE (trunk fat gain) were identified as independent markers of fat changes irrespective of the initiation of ART and the type of ART and deserve further validation.
authors.affiliation: Group of Genomics and Pharmacogenomics, Retrovirology and Viral Immunopathology Laboratory, IDIBAPS, Barcelona, Spain.
authors.forename: L
authors.initials: L
authors.lastname: Egaña-Gorroño
authors.affiliation: Department of Infectious Diseases, Hospital Clinic de Barcelona, University of Barcelona, Barcelona, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Martínez
authors.affiliation: Department of Infectious Diseases, Hospital Clinic de Barcelona, University of Barcelona, Barcelona, Spain.
authors.forename: I
authors.initials: I
authors.lastname: Pérez
authors.affiliation: Group of Genomics and Pharmacogenomics, Retrovirology and Viral Immunopathology Laboratory, IDIBAPS, Barcelona, Spain.
authors.forename: T
authors.initials: T
authors.lastname: Escribà
authors.affiliation: Department of Infectious Diseases, Hospital de Sant Pau, Barcelona, Spain.
authors.forename: P
authors.initials: P
authors.lastname: Domingo
authors.affiliation: Group of Genomics and Pharmacogenomics, Retrovirology and Viral Immunopathology Laboratory, IDIBAPS, Barcelona, Spain Department of Infectious Diseases, Hospital Clinic de Barcelona, University of Barcelona, Barcelona, Spain.
authors.forename: J M
authors.initials: JM
authors.lastname: Gatell
authors.affiliation: Group of Genomics and Pharmacogenomics, Retrovirology and Viral Immunopathology Laboratory, IDIBAPS, Barcelona, Spain marnedo@clinic.ub.es.
authors.forename: M
authors.initials: M
authors.lastname: Arnedo
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects* / Q000502:physiology*; D000328:Adult; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects / Q000639:trends*; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000188:drug therapy* / Q000453:epidemiology / Q000235:genetics*; D006801:Humans; D008060:Lipodystrophy / Q000139:chemically induced / Q000453:epidemiology / Q000235:genetics; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011446:Prospective Studies
keywords: APOE; ART; IRS1; LDLR; host genetics