Pharmacogenetics and genomics · 2025
Effects of glutathione- S -transferase polymorphisms on intravenous busulfan in hematopoietic stem cell transplant patients: a meta-analysis.
СтатьяМетаанализСистематический обзорНазвание и аннотация: Перевод в очереди
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Salman Bushra, Al Riyami Intisar, Al Maskari Raya, Al Khabori Murtadha
Аннотация
OBJECTIVE: This study examined the impact of glutathione- S -transferase polymorphisms (GSTA1, GSTM1, GSTP1, and GSTT1) on the area under the curve (AUC), clearance, veno-occlusive disease (VOD), and graft-versus-host disease (GvHD) in hematopoietic stem cell transplant (HSCT) patients treated with intravenous busulfan.
METHODS: A systematic review was performed on three electronic databases to identify relevant studies. The relative risk and the 95% confidence interval (CI) of the association of different GST polymorphisms with pharmacokinetic and clinical outcomes were reported using the random and fixed effect models. Quality of the studies was assessed using the Newcastle-Ottawa Scale for cohort studies. Heterogeneity between studies and publication bias were also carried out using R software.
RESULTS: Eighteen studies were included in the meta-analysis. GSTA1*A/*B was significantly associated with lower clearance (95% CI: 0.008-1.223, P = 0.048) and higher AUC (95% CI: -374.960 to -56.661, P = 0.008) than the GSTA1*A/*A genotype. GSTA1*B/*B had a higher busulfan AUC than GSTA1*A/*A (95% CI: -403.531 to -89.454, P = 0.002). None of the other genotypes was significantly associated with busulfan pharmacokinetic parameters or the risk of VOD or GvHD.
CONCLUSION: GSTA1 should be considered as a guide for intravenous busulfan dosing in allogeneic HSCT patients, where patients with the GSTA1*A/*A genotype require a higher dose than GSTA1*B carriers.
METHODS: A systematic review was performed on three electronic databases to identify relevant studies. The relative risk and the 95% confidence interval (CI) of the association of different GST polymorphisms with pharmacokinetic and clinical outcomes were reported using the random and fixed effect models. Quality of the studies was assessed using the Newcastle-Ottawa Scale for cohort studies. Heterogeneity between studies and publication bias were also carried out using R software.
RESULTS: Eighteen studies were included in the meta-analysis. GSTA1*A/*B was significantly associated with lower clearance (95% CI: 0.008-1.223, P = 0.048) and higher AUC (95% CI: -374.960 to -56.661, P = 0.008) than the GSTA1*A/*A genotype. GSTA1*B/*B had a higher busulfan AUC than GSTA1*A/*A (95% CI: -403.531 to -89.454, P = 0.002). None of the other genotypes was significantly associated with busulfan pharmacokinetic parameters or the risk of VOD or GvHD.
CONCLUSION: GSTA1 should be considered as a guide for intravenous busulfan dosing in allogeneic HSCT patients, where patients with the GSTA1*A/*A genotype require a higher dose than GSTA1*B carriers.