谷胱甘肽硫转移酶及乙醛脱氢酶基因多态性对环磷酰胺方案治疗膜性肾病的效果与不良反应的影响研究

Effect of Glutathione S-transferase and Aldehyde Dehydrogenase Gene Polymorphisms on the Efficacy and Adverse Reactions of Cyclophosphamide Regimen in the Treatment of Membranous Nephropathy

目的:考察谷胱甘肽硫转移酶(GST)和乙醛脱氢酶(ALDH)基因多态性对环磷酰胺(CTX)方案治疗膜性肾病的效果与不良反应的影响,为精准治疗及药学监护提供参考。方法:采用CTX方案的膜性肾病患者共65例,收集其临床资料、实验室数据及不良反应报告;采集患者全血提取DNA,以聚合酶链式反应(PCR)-直接测序法检测GSTP1 A313G(rs1695)、ALDH3A1(rs2228100)的基因型。结果:CTX方案治疗膜性肾病患者的完全缓解率为41.5%,部分缓解率为36.9%,未缓解率为21.5%。单因素分析显示,性别、体重、GSTP1 rs1695基因型对疗效存在显著影响(P=0.003;P=0.032;P=0.047);多因素分析显示,性别是疗效的独立影响因素(P=0.017)。GSTP1rs1695、ALDH3A1 rs2228100基因多态性与肝损伤或感染之间无统计学相关性。结论:GSTP1rs1695基因型对膜性肾病患者CTX方案的疗效并非独立影响因素,有待更大样本的临床研究来进一步验证。

Objective:To investigate the effects of glutathione S transferases(GST)and aldehyde dehydrogenase(ALDH)polymorphisms on the efficacy and adverse reactions of cyclophosphamide(CTX)in patients with membrane nephropathy(MN),in order to provide reference and guidance for precision treatment and pharmaceutical monitoring.Methods:A retrospective study was carried out including 65 patients with MN treated with CTX.Clinical data,laboratory data and adverse reaction reports were collected;Meanwhile,whole blood samples were collected to extract DNA for genotyping the polymorphisms of GSTP1 A313G(rs1695)and ALDH3A1 rs2228100 by a polymerase chain reaction(PCR)-direct sequencing method.Results:The complete remission rate was 41.5%,the partial remission rate was 36.9%,and the nonremission rate was 21.5%.Univariate analysis showed that gender,body weight and GSTP1(rs1695)genotype had significant effects on remission(P=0.003;P=0.032;P=0.047).In multivariate analysis,gender was an independent factor of total remission(P=0.017),GSTP1(rs1695)genotype was not an independent factor,but the difference of remission rate showed a trend that GSTP1(rs1695)A/A was more likely to have poor remission(P=0.052).No association between polymorphisms of GSTP1(rs1695)/ALDH3A1(rs2228100)and liver injury or infection was observed.Conclusion:GSTP1(rs1695)genotype may affect the efficacy of CTX regimen in patients with MN.Identification of this genotype may provide a basis for clinical individualized treatment.