title: IL-1beta (+3954C/T) polymorphism could protect human immunodeficiency virus (HIV)-infected patients on highly active antiretroviral treatment (HAART) against lipodystrophic syndrome.
abstract: OBJECTIVE
  To evaluate the impact of acquired and inherited factors on the development of lipodystrophic syndrome in patients on highly active antiretroviral therapy.
  
  
  METHODS
  Two hundred forty-three human immunodeficiency virus-infected Caucasians on highly active antiretroviral therapy were prospectively followed-up for 3 years. Eleven were naIve and 232 were on antiretrovirals (mean, 93.0 months +/- 43.8 months). Lipodystrophic syndrome was diagnosed clinically with a lipodystrophy severity grading scale. Polymorphisms of cytokines (IL-1beta, IL-6, TNF-alpha), TLR4, and NOS genes were genotyped.
  
  
  RESULTS
  Ninety (37%) patients developed lipodystrophic syndrome. The polymorphic T allele of the (+3954C/T) polymorphism of IL-1beta was less frequent in patients with lipodystrophic syndrome compared with those without (17.8% vs. 27.0%, P = 0.03). Factors significantly associated with lipodystrophic syndrome were time on stavudine (P < 0.001), use of stavudine (P = 0.001), absence of the T allele of the (+3954C/T) IL-1beta polymorphism (P = 0.02), acquired immune deficiency syndrome diagnosis (P = 0.005), nadir levels of CD4 (P = 0.003), and time on highly active antiretroviral therapy (P = 0.003). Of these factors, only the time on stavudine (hazard ratio [95% confidence intervals] 1.007 [1.001-1.013]), use of stavudine (1.678 [1.048-2.68]), and absence of the T allele of the IL-1beta (+3954C/T) polymorphism (0.569 [0.347-0.931]) were significantly associated with lipodystrophic syndrome by Cox regression.
  
  
  CONCLUSIONS
  Genotyping of the (+3954C/T) polymorphism of IL-1beta could be useful in patients starting highly active antiretroviral therapy, especially in potential users of stavudine, to predict their risk of developing lipodystrophic syndrome.
authors.affiliation: Infectious Diseases and Molecular Genetics Sections, Hospital Central de Asturias, Oviedo, Spain.
authors.forename: Victor
authors.initials: V
authors.lastname: Asensi
authors.forename: Carolina
authors.initials: C
authors.lastname: Rego
authors.forename: A Hugo
authors.initials: AH
authors.lastname: Montes
authors.forename: Julio
authors.initials: J
authors.lastname: Collazos
authors.forename: José A
authors.initials: JA
authors.lastname: Carton
authors.forename: Mónica G
authors.initials: MG
authors.lastname: Castro
authors.forename: Victoria
authors.initials: V
authors.lastname: Alvarez
authors.forename: Cristina
authors.initials: C
authors.lastname: Fernández
authors.forename: José A
authors.initials: JA
authors.lastname: Maradona
authors.forename: Eulalia
authors.initials: E
authors.lastname: Valle-Garay
mesh_terms: D023241:Antiretroviral Therapy, Highly Active; D001483:Base Sequence; D017931:DNA Primers; D015658:HIV Infections / Q000097:blood / Q000150:complications* / Q000188:drug therapy / Q000235:genetics; D006801:Humans; D053583:Interleukin-1beta / Q000235:genetics*; D008060:Lipodystrophy / Q000235:genetics* / Q000517:prevention & control; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic
chemical_list: D017931:DNA Primers; D053583:Interleukin-1beta