PMID- 15339684
OWN - NLM
STAT- MEDLINE
DCOM- 20060308
LR  - 20151119
IS  - 1592-8721 (Electronic)
IS  - 0390-6078 (Linking)
VI  - 89
IP  - 8
DP  - 2004 Aug
TI  - Analysis of human reticulocyte genes reveals altered erythropoiesis: potential 
      use to detect recombinant human erythropoietin doping.
PG  - 991-7
AB  - BACKGROUND AND OBJECTIVES: Enhancement of oxygen delivery to tissues is 
      associated with improved sporting performance. One way of enhancing oxygen 
      delivery is to take recombinant human erythropoietin (rHuEpo), which is an 
      unethical and potentially dangerous practice. However, detection of the use of 
      rHuEpo remains difficult in situations such as: i) several days after the end of 
      treatment ii) when a treatment with low doses is conducted iii) if the rHuEpo 
      effect is increased by other substances. In an attempt to detect rHuEpo abuse, we 
      selected erythroid gene markers from a SAGE library and analyzed the effects of 
      rHuEpo administration on expression of the HBB, FTL and OAZ genes. DESIGN AND 
      METHODS: Ten athletes were assigned to the rHuEpo or placebo group. The rHuEpo 
      group received subcutaneous injections of rHuEpo (50 UI/kg three times a week, 4 
      weeks; 20 UI/kg three times a week, 2 weeks). HBB, FTL and OAZ gene profiles were 
      monitored by real time-polymerase chain reaction (PCR) quantification during and 
      for 3 weeks after drug administration. RESULTS: The global analysis of these 
      targeted genes detected in whole blood samples showed a characteristic profile of 
      subjects misusing rHuEpo with a increase above the threshold levels. The 
      individual analysis of OAZ mRNA seemed indicative of rHuEpo treatment. 
      INTERPRETATION AND CONCLUSIONS: The performance-enhancing effect of rHuEpo 
      treatment is greater than the duration of hematologic changes associated with 
      rHuEpo misuse. Although direct electrophoretic methods to detect rHuEpo have been 
      developed, recombinant isoforms of rHuEpo are not detectable some days after the 
      last subcutaneous injection. To overcome these limitations indirect OFF models 
      have been developed. Our data suggest that, in the near future, it will be 
      possible to consolidate results achievable with the OFF models by analyzing 
      selected erythroid gene markers as a supplement to indirect methods.
FAU - Varlet-Marie, Emmanuelle
AU  - Varlet-Marie E
AD  - Biophysical & Bioanalysis Laboratory, Faculty of Pharmacy, University Montpellier 
      I, Montpellier, France.
FAU - Audran, Michel
AU  - Audran M
FAU - Lejeune, Mireille
AU  - Lejeune M
FAU - Bonafoux, Beatrice
AU  - Bonafoux B
FAU - Sicart, Marie-Therese
AU  - Sicart MT
FAU - Marti, Jacques
AU  - Marti J
FAU - Piquemal, David
AU  - Piquemal D
FAU - Commes, Therese
AU  - Commes T
LA  - eng
PT  - Clinical Trial
PT  - Controlled Clinical Trial
PT  - Journal Article
PL  - Italy
TA  - Haematologica
JT  - Haematologica
JID - 0417435
RN  - 0 (Biomarkers)
RN  - 0 (Placebos)
RN  - 0 (RNA, Messenger)
RN  - 0 (Recombinant Proteins)
RN  - 11096-26-7 (Erythropoietin)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Biomarkers/blood
MH  - *Doping in Sports
MH  - Erythropoiesis/*genetics
MH  - Erythropoietin/*blood
MH  - Gene Expression Regulation
MH  - Humans
MH  - Placebos
MH  - Polymerase Chain Reaction
MH  - RNA, Messenger/genetics
MH  - Recombinant Proteins
MH  - Reticulocytes/*physiology
MH  - *Sports
EDAT- 2004/09/02 05:00
MHDA- 2006/03/09 09:00
CRDT- 2004/09/02 05:00
PHST- 2004/09/02 05:00 [pubmed]
PHST- 2006/03/09 09:00 [medline]
PHST- 2004/09/02 05:00 [entrez]
PST - ppublish
SO  - Haematologica. 2004 Aug;89(8):991-7.