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


CONCLUSIONS
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.
Schneider
Uffe V
UV
Clinical Research Centre, Copenhagen University Hospital, Hvidovre, Denmark. uvs@get2net.dk
Nielsen
Rikke L
RL
Pedersen
Court
C
Eugen-Olsen
Jesper
J
D000328:Adult; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D004279:DNA, Viral / Q000097:blood; D003718:Denmark / Q000453:epidemiology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015658:HIV Infections / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality*; D015497:HIV-1 / Q000187:drug effects / Q000302:isolation & purification*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D011237:Predictive Value of Tests; D011336:Probability; D011379:Prognosis; D011401:Promoter Regions, Genetic; D011956:Receptors, Cell Surface / Q000097:blood* / Q000235:genetics*; D055293:Receptors, Urokinase Plasminogen Activator; D012189:Retrospective Studies; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D018709:Statistics, Nonparametric; D016019:Survival Analysis
D015415:Biomarkers; D004279:DNA, Viral; C524898:PLAUR protein, human; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator