Submit Data |  Help |  Video Tutorials |  News |  Publications |  FTP Download |  REST API |  Citing RGD |  Contact   

Glutathione S-transferase M1 polymorphism: a risk factor for hepatic venoocclusive disease in bone marrow transplantation.

Authors: Srivastava, A  Poonkuzhali, B  Shaji, RV  George, B  Mathews, V  Chandy, M  Krishnamoorthy, R 
Citation: Srivastava A, etal., Blood. 2004 Sep 1;104(5):1574-7. Epub 2004 May 13.
Pubmed: (View Article at PubMed) PMID:15142875
DOI: Full-text: DOI:10.1182/blood-2003-11-3778

Hepatic venoocclusive disease (HVOD) in bone marrow transplantation (BMT) is attributed to toxicity of cytoreductive agents, especially busulfan and cyclophosphamide, in the conditioning therapy. Busulfan, as well as the metabolites of cyclophosphamide, are conjugated with glutathione (GSH), catalyzed by enzymes of the glutathione S-transferase (GST) family. To assess the impact of polymorphisms of the GST genes, GSTM1 and GSTT1, on the risk of HVOD, we evaluated 114 consecutive patients with beta-thalassemia major undergoing BMT. There was a significantly increased incidence of HVOD in patients with the GSTM1-null genotype compared with those with the GSTM1-positive genotype (46.5% vs 18.3%; P =.001). Pharmacokinetic analysis in these patients showed that the clearance of busulfan was higher and first-dose steady-state concentration was lower among those with HVOD (0.403 +/- 0.06 vs 0.33 +/- 0.071 L/h/kg, Student t test P value =.000 01; and 508 +/- 125 vs 656 +/- 255 ng/mL, t test P value =.001, respectively). We conclude that the GSTM1-null genotype predisposes to HVOD, and the sinusoidal endothelial cells and hepatocyte damage may be mediated by metabolites of busulfan through depletion of the cellular GSH pool.

Annotation

Disease Annotations
Objects Annotated

Additional Information

 
CRRD Object Information
CRRD ID: 10450877
Created: 2016-01-22
Species: All species
Last Modified: 2016-01-22
Status: ACTIVE



NHLBI Logo

RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.