摘要
目的研究人体内参与沙利度胺代谢的 CYP2C19基因多态性在多发性骨髓瘤(MM)中的分布以及对含沙利度胺方案治疗 MM 疗效的影响,探讨抗血管生成在 MM 治疗中的作用。方法采用 PCR-限制性片段长度多态性(PCR-RFLP)方法检测92例 MM 患者的 CYP2C19基因型,观察弱代谢型(PM)在中国人 MM 患者中的发生率,比较强代谢型(EM)和 PM 患者经沙利度胺治疗后的有效率。结果 92例 MM 患者中 PM 18例(19.5%),与健康汉族人中 PM 的发生率相当;EM 和 PM 患者治疗后的有效率分别为62.6%和33.3%,差异有统计学意义(P<0.05);按治疗方案分组后,沙利度胺联合地塞米松组中 EM 和 PM 有效率分别为60.8%和27.3%,差异有统汁学意义(P<0.05);沙利度胺联合传统化疗组 EM 有效率(65.2%)高于 PM(42.7%),但差异无统计学意义。结论 CYP2C19基因多态性与 MM 的发生无明显相关性,但影响沙利度胺的药效,PM 患者有效率较低可能与沙利度胺抗血管生成作用减弱有关。
Objective To study the distribution of different genotypes of CYP2C19 in multiple myeloma （ MM）, and investigate the effect of its polymorphism on efficacy of thalidomide-based regimens for the treatment of MM and discuss the role of antiangiogenesis in MM. Methods The CYP2C19 genotype of 92 patients with multiple myeloma was determined by polymerase chain reaction-restriction fragment length polymorphism （PCR-RFLP）. The incidence of poor metabolizer （PM） in MM was compared with that in healthy Chinese people. After they were treated with thalidomide-based regimens, the response rate was compared between extensive metabolizers （EMs） and PMs. Results Of 92 patients, 18 （ 19.5% ） were PMs, which was comparable to that in healthy ones. The response rates in EMs and PMs were 62.6% and 33.3% , respectively （ P 〈 0.05 ）. When patients were grouped by treatment regimens, the response rate in EMs was significant- ly higher than that in PMs （ 60.8% vs. 27.3% ） for the thalidomide-dexamethasone group, and similar results were observed for the thalidomide-chemotherapy group （65.2% vs. 42.7% ） though there was no statistical difference （ P 〉 0.05 ）. Conclusion CYP2C19 genotype has no difference between MM patients and healthy person, but exhibits an effect on the treatment efficacy of thalidomide for MM. The lower response rate observed in PMs is possibly due to the reduced activity to inhibit angiogenesis by thalidomide.
出处
《中华血液学杂志》
CAS
CSCD
北大核心
2007年第10期651-654,共4页
Chinese Journal of Hematology
