title: Erythropoietin rs1617640 G allele associates with an attenuated rise of serum erythropoietin and a marked decline of hemoglobin in hepatitis C patients undergoing antiviral therapy.
abstract: BACKGROUND
  A decline in hemoglobin (Hb) concentration during antiviral therapy in chronic hepatitis C (CHC) is a serious side effect. It may compel to dose reduction or even termination of antiviral treatment. The activation of erythropoietin (EPO) synthesis as a physiological response to anemia and its relation to a genetic variation within the EPO gene has not been evaluated yet.
  
  
  METHODS
  Data of 348 CHC patients were reviewed retrospectively. Samples were genotyped for EPO rs1617640 and inosine triphosphatase (ITPA) rs1127354. Serum EPO concentrations were determined before and during therapy. Primary endpoints were set as Hb decline >3 g/dl at weeks 4 and 12.
  
  
  RESULTS
  EPO rs1617640 G homozygotes showed a significantly lower rise of serum EPO level over time than T allele carriers (p < 0.001). The cumulative frequency of a significant Hb reduction added up to 40%. Multivariate analysis revealed that besides age, ribavirin starting dose and baseline Hb also EPO rs1617640 G homozygosity associates with Hb reduction at week 4 (p = 0.025) and 12 (p = 0.029), while ITPA C homozygotes are at risk for Hb decline particularly early during treatment. Furthermore, EPO rs1617640 G homozygotes were more frequently in need for blood transfusion, epoetin-α supplementation, or ribavirin dose reduction (p < 0.001).
  
  
  CONCLUSIONS
  Our data suggest that EPO rs1617640 genotype, the rise of serum EPO concentration as well as ITPA rs1127354 genotype are promising parameters to evaluate the Hb decline during antiviral therapy. A rational adjustment of therapy with epoetin-α supplementation might prevent serious adverse events or the need to terminate treatment.
authors.affiliation: Department of Gastroenterology and Endocrinology, University Medical Center Goettingen, Robert-Koch-Strasse 40, 37075 Goettingen, Germany. ahmad.amanzada@med.uni-goettingen.de.
authors.forename: Ahmad
authors.initials: A
authors.lastname: Amanzada
authors.forename: Armin D
authors.initials: AD
authors.lastname: Goralczyk
authors.forename: Lars
authors.initials: L
authors.lastname: Reinhardt
authors.forename: Federico
authors.initials: F
authors.lastname: Moriconi
authors.forename: Silke
authors.initials: S
authors.lastname: Cameron
authors.forename: Sabine
authors.initials: S
authors.lastname: Mihm
mesh_terms: D000328:Adult; D000483:Alleles; D000998:Antiviral Agents / Q000627:therapeutic use*; D015536:Down-Regulation; D000068817:Epoetin Alfa; D004921:Erythropoietin / Q000097:blood* / Q000235:genetics*; D005260:Female; D005838:Genotype; D006454:Hemoglobins / Q000378:metabolism*; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000097:blood / Q000188:drug therapy* / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011755:Pyrophosphatases / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins; D012189:Retrospective Studies; D012254:Ribavirin / Q000627:therapeutic use; D016896:Treatment Outcome; D000097630:Inosine Triphosphatase
chemical_list: D000998:Antiviral Agents; D000068817:Epoetin Alfa; D004921:Erythropoietin; D006454:Hemoglobins; D011755:Pyrophosphatases; D011994:Recombinant Proteins; D012254:Ribavirin; C511829:ITPA protein, human; D000097630:Inosine Triphosphatase