Erythropoietin in the general population: reference ranges and clinical, biochemical and genetic correlates.
BACKGROUND
Although erythropoietin has been used for decades in the treatment of anemia, data regarding endogenous levels in the general population are scarce. Therefore, we determined erythropoietin reference ranges and its clinical, biochemical and genetic associations in the general population.


METHODS
We used data from 6,777 subjects enrolled in the Prevention of REnal and Vascular ENd-stage Disease (PREVEND) study. Fasting venous blood samples were obtained in the morning from all participants from 2001-2003. Serum erythropoietin concentrations were measured using a fully automated chemiluminescent enzyme-labeled immunometric assay. A genome-wide association study was performed to identify genetic determinants.


RESULTS
Mean age (± SD) was 53 ± 12 years and 50% were female. Median (IQR) erythropoietin concentrations were 7.6 (5.8-9.9) IU/L in men and 7.9 (6.0-10.6) IU/L in women. A strong positive correlation was found between erythropoietin and waist circumference, glucose and systolic blood pressure (all P < 0.05). In subjects with normal renal function there was a strong exponential relation between hemoglobin and erythropoietin, whereas in renal impairment (eGFR < 60 mL/min/1.73m²) this relation was linear (men) or absent (women) (P < 0.001 for interaction). Single-nucleotide polymorphisms at the HBS1L-MYB locus were shown to be related to erythropoietin levels (P < 9x10-21), more significantly than other erythrocyte parameters.


CONCLUSIONS
We provide age-specific reference ranges for endogenous serum erythropoietin. Erythropoietin levels are positively associated with the components of the metabolic syndrome, except cholesterol. We show that even mild renal failure blunts erythropoietin production and propose the HBS1L-MYB locus as a regulator of erythropoietin.
Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Niels
N
Grote Beverborg
Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Niek
N
Verweij
Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Ijsbrand T
IT
Klip
Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Haye H
HH
van der Wal
Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Adriaan A
AA
Voors
Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Dirk J
DJ
van Veldhuisen
Department of Nephrology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Ron T
RT
Gansevoort
Department of Nephrology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Stephan J L
SJ
Bakker
Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Pim
P
van der Harst
Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Peter
P
van der Meer
D000328:Adult; D000367:Age Factors; D000368:Aged; D004797:Enzyme-Linked Immunosorbent Assay; D004921:Erythropoietin / Q000097:blood* / Q000235:genetics; D005260:Female; D055106:Genome-Wide Association Study; D006801:Humans; D007674:Kidney Diseases / Q000097:blood; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012016:Reference Values; D012737:Sex Factors
D004921:Erythropoietin