title: Pharmacogenetic analysis of liver toxicity after busulfan/cyclophosphamide-based allogeneic hematopoietic stem cell transplantation.
abstract: THE AIM of this study was to evaluate the impact of genomic polymorphisms of methylene-tetrahydrofolate-reductase (MTHFR-C677T, MTHFR-A1298C) and various glutathione S-transferases (GSTP1-Ilel05Val, GSTA1*a/b, GSTM1, GSTT1) on the occurrence of liver toxicity in patients receiving allogeneic hematopoietic stem cell transplantation (HSCT).
  
  
  METHODS
  Eighty-four adult patients were enrolled in this retrospective study. All patients were treated with busulfan/cyclophosphamide as a conditioning regimen and received cyclosporine and short-course MTX for GvHD prophylaxis. Genotyping was performed using PCR based restriction-fragment-length-polymorphism (RFLP) techniques.
  
  
  RESULTS
  Multivariate analysis identified the MTHFR-A1298C polymorphism as an independent predictor for maximum levels of bilirubin (p=0.0025) and duration of hyperbilirubinaemia (p=0.013). Furthermore, there was an association between this polymorphism and the occurrence of the sinusoidal obstruction syndrome (SOS) (p=0.048). No significant associations between the MTHFR-C677T or the various GST polymorphisms and liver toxicity were observed.
  
  
  CONCLUSIONS
  The MTHFR-A1298C polymorphism might be associated with liver toxicity in patients receiving allogeneic HSCT.
authors.affiliation: Department of Internal Medicine I, University Hospital Carl Gustav Carus, University Dresden, Germany. eray.goekkurt@uniklinikum-dresden.de
authors.forename: Eray
authors.initials: E
authors.lastname: Goekkurt
authors.forename: Jan
authors.initials: J
authors.lastname: Stoehlmacher
authors.forename: Christian
authors.initials: C
authors.lastname: Stueber
authors.forename: Christine
authors.initials: C
authors.lastname: Wolschke
authors.forename: Thomas
authors.initials: T
authors.lastname: Eiermann
authors.forename: Simona
authors.initials: S
authors.lastname: Iacobelli
authors.forename: Axel R
authors.initials: AR
authors.lastname: Zander
authors.forename: Gerhard
authors.initials: G
authors.lastname: Ehninger
authors.forename: Nicolaus
authors.initials: N
authors.lastname: Kröger
mesh_terms: D000293:Adolescent; D000328:Adult; D002066:Busulfan / Q000009:adverse effects*; D056486:Chemical and Drug Induced Liver Injury; D003520:Cyclophosphamide / Q000009:adverse effects*; D005260:Female; D005982:Glutathione Transferase / Q000235:genetics; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D008099:Liver / Q000187:drug effects; D008107:Liver Diseases / Q000235:genetics*; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics; D008875:Middle Aged; D019653:Myeloablative Agonists / Q000009:adverse effects*; D010597:Pharmacogenetics; D012150:Polymorphism, Restriction Fragment Length; D012189:Retrospective Studies; D019172:Transplantation Conditioning / Q000009:adverse effects*; D014184:Transplantation, Homologous
chemical_list: D019653:Myeloablative Agonists; D003520:Cyclophosphamide; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D005982:Glutathione Transferase; D002066:Busulfan