Department of Clinical Hematology, Key Laboratory of Laboratory Medical Diagnostics Designated by the Ministry of Education, Chongqing Medical University, No. 1, Yixueyuan Road, Chongqing, 400016, PR China.
Pharmacogenomics. 2014 Apr;15(5):667-77. doi: 10.2217/pgs.13.222.
MDR1 gene polymorphisms were demonstrated to be associated with interindividual variability of imatinib response for chronic myeloid leukemia (CML) patients in several studies; however, the results have been inconclusive.
MATERIALS & METHODS: To clarify the effect of common MDR1 variants on clinical response to imatinib, we performed a meta-analysis to quantify the accumulated information from genetic association studies. After a thorough search of the published literature, we undertook a meta-analysis to evaluate the effect of MDR1 C1236T, G2677T and C3435T polymorphisms on imatinib response.
Our pooled data showed a significant association between MDR1 C1236T polymorphism and the increasing risk of imatinib resistance in Asian CML patients. However, no significant association was found for the MDR1 G2677T or C3435T polymorphisms in an Asian CML population as well as a Caucasian CML population.
The synonymous MDR1 C1236T polymorphism might be a risk factor for nonoptimal clinical response to imatinib in Asian CML patients.
多项研究表明,MDR1 基因多态性与慢性髓性白血病(CML)患者对伊马替尼反应的个体间差异有关;然而,结果尚无定论。
为了阐明常见 MDR1 变异对伊马替尼临床反应的影响,我们进行了荟萃分析,以量化来自遗传关联研究的累积信息。在彻底搜索已发表文献后,我们进行了荟萃分析,以评估 MDR1 C1236T、G2677T 和 C3435T 多态性对伊马替尼反应的影响。
我们的汇总数据显示,MDR1 C1236T 多态性与亚洲 CML 患者伊马替尼耐药风险增加之间存在显著关联。然而,在亚洲 CML 人群以及高加索 CML 人群中,均未发现 MDR1 G2677T 或 C3435T 多态性与伊马替尼耐药之间存在显著关联。
同义 MDR1 C1236T 多态性可能是亚洲 CML 患者对伊马替尼临床反应不理想的一个危险因素。