GSTP1(rs1695)基因多态性与自体造血干细胞移植患者血液学毒性的关系研究

Study on the Relationship of GSTP1(rs1695) Genetic Polymorphism with Hematological Toxicity of Autologous Hematopoietic Stem Cell Transplantation Patients

目的:研究GSTP1(rs1695)(简称GSTP1)基因多态性与自体造血干细胞移植患者使用CBV方案(环磷酰胺、卡莫司汀、依托泊苷)预处理后血液学毒性之间的关系。方法:对2015年4月-2017年6月到我院治疗的83例使用CBV方案预处理的自体造血干细胞移植患者进行回顾性分析,采用荧光染色原位杂交检测法测定GSTP1 A313G的多态性,统计血液学毒性和粒细胞缺乏性发热发生率以及白细胞、中性粒细胞、血小板植入时间,分析GSTP1基因与上述指标之间的关系。结果:83例患者中28例(33.73%)存在有至少1个基因位点的变异,A等位基因频率为81.3%,G等位基因频率为18.7%。GSTP1 AA基因型患者发生Ⅳ度白细胞、Ⅳ度中性粒细胞、Ⅳ度血小板减少的时间分别为化疗后(8.91±1.25)、(9.02±1.19)、(11.56±1.58)d,携带GSTP1 313等位基因G(AG/GG基因型)的患者减少的时间分别为化疗后(8.61±1.17)、(8.68±1.19)、(11.44±1.34)d。GSTP1 AA基因型患者白细胞、中性粒细胞、血小板的植入时间分别为自体造血干细胞回输后(11.98±1.99)、(10.44±1.35)、(15.55±2.18)d;携带GSTP1 313等位基因G(AG/GG基因型)的患者植入时间分别为自体造血干细胞回输后(12.41±2.44)、(10.36±1.62)、(16.29±3.15)d。GSTP1 AA基因型及携带GSTP1 313等位基因G(AG/GG基因型)的患者移植期间发生Ⅲ~Ⅳ度贫血的患者分别为24、11例,分别占对应基因型患者的43.64%、39.29%;发生粒细胞缺乏性发热的分别为21、11例,分别占对应基因型患者的38.18%、39.29%,但上述差异均无统计学意义(P>0.05)。结论:GSTP1基因多态性与自体造血干细胞移植患者使用CBV方案预处理后的血液学毒性未见相关性,亦不影响干细胞植入时间。

OBJECTIVE:To study the relationship of GSTP1(rs1695)(simply as GSTP1)gene polymorphism with the hematological toxicity in autologous hematopoietic stem cell transplantation(AHSCT)patients who used CBV regimen(cyclophosphamide,carmustine,etoposide).METHODS:A total of 83 AHSCT patients receiving CBV regimen were retrospective analyzed in our hospital during Apr.2015-Jun.2017.The gene polymorphism of GSTP1 A313G was detected by fluorescence staining in situ hybridization.The hematological toxicity and the incidence of agranulocytosis fever,the implantation time of leukocyte,neutrophils and platelet were analyzed statistically.The relationship of GSTP1 with above indexes were analyzed.RESULTS:Among 83 patients,gene variation was observed in one gene loci at least of 28 patients(33.73%).The gene frequency of A allele was 81.3%,while that of G allele was 18.7%.The reduce time ofⅣgrade leukopenia,Ⅳgrade neutropenia andⅣgrade thrombocytopenia in GSTP1 AA genotype patients were(8.91±1.25),(9.02±1.19),(11.56±1.58)d after chemotherapy;those of patients with GSTP1 313 allele G(AG/GG genotype)were(8.61±1.17),(8.68±1.19),(11.44±1.34)d after chemotherapy.The implantation time of leukocyte,neutrophils and platelet in patients with GSTP1 AA genotype were(11.98±1.99),(10.44±1.35),(15.55±2.18)d after autologus peripheral blood stem cell reinfusion;those of patients with GSTP1 313 allele G(AG/GG genotype)were(12.41±2.44),(10.36±1.62),(16.29±3.15)d after autologus peripheral blood stem cell reinfusion.The case number of gradeⅢ-Ⅳanemia were 24 and 11,accounting for 43.64%and 39.29%of corresponding genotype patients.The case number of agranulocytosis fever in patients with GSTP1 AA genotype or GSTP1 313 allele G(AG/GG genotype)were 21 and 11 during transplantation,accounting for 38.18%and 39.29%of corresponding genotype patients,respectively,without statistical significantly(P>0.05).CONCLUSIONS:There is no relationship between GSTP1 gene polymorphism and hematological toxicity of AHSCT patients receiving CBV regimen.