摘要
目的:研究急性白血病(acute leukemia,AL)患者中,细胞色素P4503A亚家族多肽5(cytochrome P450,subfamilyⅢA,polypeptide 5,CYP3A5)多态性、酶活性对患者发病、疗效和预后的影响。方法:采用PCR-限制性片段长度多态性(PCR-restriction fragment length polymorphism,PCR-RFLP)分析法,检测AL患者骨髓原代细胞CYP3A5*3突变频率,并应用高效液相色谱法(high performance liquid chromatography,HPLC)检测AL患者骨髓原代细胞CYP3A5酶的活性。结果:88例样本中野生型纯合子(CYP3A5*1/*1)23例(26%),杂合子(CYP3A5*1/*3)44例(50%),突变型纯合子(CYP3A5*3/*3)21例(24%)。CYP3A5*3等位基因频率为74%,符合中国健康人群分布。按基因型分组后,3组的临床资料差异无统计学意义;3组的CYP3A5酶活性[以6β-羟基氢化可的松(6β-hydroxycortisol,6β-OHC)/氢化可的松(hydrocortisone,HC)值表示]检测结果分别为1.344±0.027、0.120±0.067和0.014±0.001;总生存率分别为(11.6±2.1)个月、(30.5±12.2)个月和(52.3±8.5)个月;无病生存期分别为(7.5±1.8)个月、(27.0±15.8)个月和(52.3±8.1)个月;差异均有统计学意义。结论:CYP3A5*3突变与AL发病无关,但可使CYP3A5酶活性显著降低或消失。含CYP3A5*1等位基因与耐药显著相关,从而影响患者的化疗疗效和预后。对初治AL患者进行CYP3A5基因分型和酶活性检测可以作为预测AL患者个体化治疗和预后的重要指标。
Objective：To study the effect of the polymorphism and enzyme activity of CYP3A5 （cytochrome P450, subfamily ⅢA, polypeptide 5） on the morbidity, clinical outcome, and prognosis of acute leukemia （AL） patients. Methods： The polymorphism of CYP3A5 gene was detected by polymerase chain reaction restriction fragment length polymorphism （PCR-RFLP） in cultured primary bone marrow cells and the CYP3A5 enzyme activity was measured by high performance liquid chromatography （HPLC）. Results：There were three CYP3A5 genotypes in the 88 cases, namely CYP3A51/1, CYP3A51/3, and CYP3A53/ 3 with frequencies of 26% （n=23）, 50% （n=44）, and 24% （n=21）, respectively. The allele frequency of CYP3A53 was 74%, which was in accordance with the distribution of healthy Chinese population. There were no significant differences in clinic data between the three groups, but the CYP3A5 enzyme activity （signed as 6β-hydroxycortisol / hydrocortisone of three groups were 1.344±0.027, 0.120±0.067, and 0.014±0.001; the overall survival were （7.5±1. 8）, （30.5±12.2）, and （52.3±8.5） months, respectively; and the disease-free survival were （7.5±1.8）, （27.0±15.8）, and （52.3±8.1） months, respectively. The difference was significant （P〈0.05）. Conclusion： Mutation of CYP3A53 has no correlation with the incidence of AL but causes significant decrease or loss in CYP3A5 enzyme activity. CYP3A51 allele is closely associated with the drug-resistance, which markedly affects the chemotherapeutic efficacy and the prognosis of AL patients. So detection of the CYP3A5 genotype and enzyme activity may be used as an important index for predicting the individual clinical outcome and the prognosis of AL patients.
出处
《肿瘤》
CAS
CSCD
北大核心
2009年第3期259-264,共6页
Tumor
基金
国家自然科学基金资助项目(编号:30400183)
