GSTA1基因多态性与白消安为基础预处理方案致急性肝损伤的相关性研究

Association Study of GSTA1 Genetic Polymorphisms and Acute Liver Injury Induced by Busulfan-based Preparative Regimens

目的探讨GSTA1基因多态性与以白消安为基础预处理的造血干细胞移植人群发生急性肝损伤的相关性。方法收集以白消安为基础的预处理的HSCT患者115例,PCR-RFLP法测定样本GSTA1 C-69T基因多态性,MALDI-TOF-MS法验证,经χ^(2)检验分析基因型与急性肝损伤相关性。结果GSTA1*A/*A(野生型)、*A/*B(杂合型)、*B/*B(纯突变表型)基因型频率分别为80.9%、19.1%、0%,该分布符合Hardy-Weinberg平衡;该基因型与急性肝损伤的发生存在相关性(χ^(2)=5.222,P=0.022,RR=2.416,95%CI:1.160-5.032)。结论携带GSTA1*A/*B(杂合型)的患者急性肝损伤的发生率显著高于携带GSTA1*A/*A(野生型)的患者,有必要对Bu实行个体化给药并对携带GSTA1*B等位基因的患者加强监测和保护。

Objective To investigate the association of GSTA1 Genetic Polymorphisms and acute liver injury induced by busulfan-based preparative regimens for HSCT.Methods One hundred and fifteen HSCT patients who underwent busulfan-based pretreatment were collected,GSTA1 C-69T polymorphisms were detemined by PCR-RFLP,and were checked by TMALDI-TOF-MS,the association of GSTA1 genotypes and acute liver injury was analysised by chi square test.Results The genetype frequencies of GSTA1*A/*A,*A/*B,*B/*B were 80.9%,19.1%,0%,the distribution conformed to Hardy-Weinberg Equilibrium;there was an significant association between GSTA1 C-69T polymorphisms and acute liver injury(χ^(2)=5.222,P=0.022,RR=2.416,95%CI:1.160-5.032).Conclusion The incidence of acute liver injury in patients with GSTA1*A/*B was significantly higher than that in patients with GSTA1*A/*A,individualized administration of Bu is necessary,and strengthen monitoring and protection is suggested in the patients with GSTA1*B allele.