title: TNF-alpha promoter region gene polymorphisms in HIV-positive patients with lipodystrophy.
abstract: OBJECTIVE
  The pathogenic mechanisms underlying lipodystrophy in HIV-positive patients are largely unknown. TNF-alpha has many actions that are consistent with the features of lipodystrophy; therefore, an analysis was carried out to determine whether functionally active polymorphisms in the promoter region of the TNF-alpha gene are associated with the development of lipodystrophy.
  
  
  METHODS
  Genetic case-control association study.
  
  
  METHODS
  Individuals were genotyped for the -238 and -308 polymorphisms in the TNF-alpha gene using polymerase chain reaction-restriction fragment length polymorphism analysis. The genotype and allele frequencies for 61 HIV-positive patients with lipodystrophy were compared with (a) 35 HIV-positive patients with no evidence of lipodystrophy and (b) 239 healthy HIV-negative individuals.
  
  
  RESULTS
  The frequency of the variant rare -238 allele was significantly different (P = 0.01) in HIV-positive patients with lipodystrophy than in those without lipodystrophy. At the genotype level, a trend towards a difference between patients with and without lipodystrophy was observed (chi2 for linear trend 5.2, P = 0.02). For the -308 polymorphism, no difference was found in genotype and allele frequencies between HIV patients with and without lipodystrophy.
  
  
  CONCLUSIONS
  The data suggest that the -238 (but not the -308) promoter region TNF-alpha gene polymorphism is a determinant in the development of HIV-related lipodystrophy. However, the results need to be confirmed in larger numbers of patients as well as in an ethnically diverse population.
authors.affiliation: Department of Pharmacology, The University of Liverpool, Ashton Street, Liverpool, UK.
authors.forename: Bridget
authors.initials: B
authors.lastname: Maher
authors.forename: Ana
authors.initials: A
authors.lastname: Alfirevic
authors.forename: F Javier
authors.initials: FJ
authors.lastname: Vilar
authors.forename: Edmund G L
authors.initials: EG
authors.lastname: Wilkins
authors.forename: B Kevin
authors.initials: BK
authors.lastname: Park
authors.forename: Munir
authors.initials: M
authors.lastname: Pirmohamed
mesh_terms: D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D015658:HIV Infections / Q000188:drug therapy / Q000235:genetics; D018023:HIV Seronegativity / Q000235:genetics; D039682:HIV-Associated Lipodystrophy Syndrome / Q000188:drug therapy / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
chemical_list: D014409:Tumor Necrosis Factor-alpha