The prognostic value of the suPARnostic ELISA in HIV-1 infected individuals is not affected by uPAR promoter polymorphisms

BMC Infect Dis. 2007 Nov 16:7:134. doi: 10.1186/1471-2334-7-134.

Abstract

Background: High blood levels of soluble urokinase Plasminogen Activator Receptor (suPAR) are associated with poor outcomes in human immunodeficiency-1 (HIV-1) infected individuals. Research on the clinical value of suPAR in HIV-1 infection led to the development of the suPARnostic(R) assay for commercial use in 2006. The aim of this study was to: 1) Evaluate the prognostic value of the new suPARnostic assay and 2) Determine whether polymorphisms in the active promoter of uPAR influences survival and/or suPAR values in HIV-1 patients who are antiretroviral therapy (ART) naive.

Methods: DNA samples were collected retrospectively from 145 Danes infected with HIV-1 with known seroconversion times. In addition, plasma was collected retrospectively from 81 of these participants for use in the suPAR analysis. Survival was analysed using Kaplan Meier analysis.

Results: Survival was strongly correlated to suPAR levels (p < 0.001). Levels at or above 6 ng/ml were associated with death in 13 of 27 patients within a two-years period; whereas only one of 54 patients with suPAR levels below 6 ng/ml died during this period. We identified two common uPAR promoter polymorphisms: a G to A transition at -118 and an A to G transition at -465 comparative to the transcription start site. These promoter transitions influenced neither suPAR levels nor patient survival.

Conclusion: Plasma suPAR levels, as measured by the suPARnostic(R) assay, were strongly predictive of survival in ART-naïve HIV-1 infected patients. Furthermore, plasma suPAR levels were not influenced by uPAR promoter polymorphisms.

MeSH terms

  • Adult
  • Antiretroviral Therapy, Highly Active / methods
  • Biomarkers / blood
  • Case-Control Studies
  • DNA, Viral / blood
  • Denmark / epidemiology
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • HIV Infections / diagnosis
  • HIV Infections / drug therapy
  • HIV Infections / genetics*
  • HIV Infections / mortality*
  • HIV-1 / drug effects
  • HIV-1 / isolation & purification*
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Polymorphism, Genetic*
  • Polymorphism, Restriction Fragment Length
  • Predictive Value of Tests
  • Probability
  • Prognosis
  • Promoter Regions, Genetic
  • Receptors, Cell Surface / blood*
  • Receptors, Cell Surface / genetics*
  • Receptors, Urokinase Plasminogen Activator
  • Retrospective Studies
  • Risk Assessment
  • Sensitivity and Specificity
  • Statistics, Nonparametric
  • Survival Analysis

Substances

  • Biomarkers
  • DNA, Viral
  • PLAUR protein, human
  • Receptors, Cell Surface
  • Receptors, Urokinase Plasminogen Activator