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Association of CTH variant with sinusoidal obstruction syndrome in children receiving intravenous busulfan and cyclophosphamide before hematopoietic stem cell transplantation.


ABSTRACT: Sinusoidal obstruction syndrome (SOS) is a severe complication of hematopoietic stem cell transplantation (HSCT) that can be fatal, often attributed to the conditioning regimen prior to HSCT. We evaluated the association of SOS risk with gene variants in cystathionase (CTH), an enzyme involved in glutathione synthesis, in 76 children receiving intravenous busulfan (Bu) before HSCT. Our results indicated an association with CTHc.1364 G>T (ORTT=10.6, 95% confidence interval (CI)=2.16, 51.54) and SOS risk, which was sex dependent (female patients, ORTT=21.82, 95% CI=3.590-132.649). The interaction between CTHc.1364 G>T and another risk variant (GSTA1*B) was explored. A recessive model with the use of GSTA1*B*B and CTH c.1364 TT genotypes proved to be useful at predicting SOS occurrence, indicating the possibility of using these gene variants as markers of SOS occurrence and to further individualize preemptive treatment aimed at reducing SOS incidence.

SUBMITTER: Huezo-Diaz Curtis P 

PROVIDER: S-EPMC5817388 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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Association of CTH variant with sinusoidal obstruction syndrome in children receiving intravenous busulfan and cyclophosphamide before hematopoietic stem cell transplantation.

Huezo-Diaz Curtis P P   Uppugunduri C R S CRS   Muthukumaran J J   Rezgui M A MA   Peters C C   Bader P P   Duval M M   Bittencourt H H   Krajinovic Maja M   Ansari Marc M  

The pharmacogenomics journal 20161025 1


Sinusoidal obstruction syndrome (SOS) is a severe complication of hematopoietic stem cell transplantation (HSCT) that can be fatal, often attributed to the conditioning regimen prior to HSCT. We evaluated the association of SOS risk with gene variants in cystathionase (CTH), an enzyme involved in glutathione synthesis, in 76 children receiving intravenous busulfan (Bu) before HSCT. Our results indicated an association with CTHc.1364 G>T (OR<sub>TT</sub>=10.6, 95% confidence interval (CI)=2.16, 5  ...[more]

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