CYP2C19基因多态性对沙利度胺治疗多发性骨髓瘤疗效的影响

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PM18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％，差异有统计学意义（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。

Effect of CYP2C19 gene polymorphism on efficacy of thalidomide-based regimens for the treatment of multiple myeloma

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 significantly 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.