Department of Pharmaceutical Sciences and Interdepartmental Research Center of Pharmacogenetics and Pharmacogenomics (CRIFF), University of Piemonte Orientale, Novara, Italy.
Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy.
Pharmacol Res. 2018 May;131:244-254. doi: 10.1016/j.phrs.2018.02.005. Epub 2018 Feb 7.
Contrasting results have been reported on the role of rs628031 and rs683369 polymorphisms of SLC22A1 and rs776746 of CYP3A5 on imatinib treatment response in patients with chronic myeloid leukemia (CML). In the present study, we conducted a systematic review and meta-analysis of published studies to estimate the impact of the above-mentioned gene variants on major molecular response (MMR) or complete cytogenetic response (CCyR) in imatinib-treated CML patients. We performed a comprehensive search through PubMed, Web of Knowledge, and Cochrane databases up to September 2017. The pooled analyses showed association between carriers of SLC22A1 rs628031A allele (GA + AA vs GG, OR: 0.58, 95% CI: 0.38-0.88, P = 0.011) or rs683369G allele (CG + GG vs CC, OR: 0.64, 95% CI: 0.42-0.96, P = 0.032) and a lower MMR rate. The combined analyses also revealed a correlation between the dominant (GG + AG vs AA, OR: 2.43, 95%CI: 1.12-5.27, P = 0.024) or the allelic model (G vs A, OR: 1.72, 95% CI: 1.09-2.72, P = 0.020) of CYP3A5 rs776746 with higher CCyR rates. The subsequent sensitivity analysis confirmed the statistical significance of CYP3A5 rs776746 among Asian CML patients (dominant model OR: 3.90; 95%CI: 2.47-6.14, P < 0.001; allelic model OR: 2.08; 95% CI: 1.47-2.95, P < 0.001). In conclusion, the present meta-analysis supports the association of SLC22A1 and CYP3A5 genotypes with clinical imatinib response rates of CML patients, nevertheless further large studies, particularly in Caucasians, are still warranted to provide conclusive evidences.
SLC22A1 的 rs628031 和 rs683369 多态性以及 CYP3A5 的 rs776746 多态性对慢性髓性白血病 (CML) 患者伊马替尼治疗反应的作用已有报道，但结果不尽相同。本研究通过系统评价和荟萃分析，对上述基因变异与伊马替尼治疗的 CML 患者主要分子反应 (MMR) 或完全细胞遗传学反应 (CCyR) 的相关性进行评估。我们通过 PubMed、Web of Knowledge 和 Cochrane 数据库进行了全面检索，检索截止日期为 2017 年 9 月。汇总分析显示，SLC22A1 rs628031A 等位基因（GA+AA 与 GG，OR：0.58，95%CI：0.38-0.88，P=0.011）或 rs683369G 等位基因（CG+GG 与 CC，OR：0.64，95%CI：0.42-0.96，P=0.032）携带者的 MMR 率较低。合并分析还显示，CYP3A5 rs776746 显性（GG+AG 与 AA，OR：2.43，95%CI：1.12-5.27，P=0.024）或等位基因模型（G 与 A，OR：1.72，95%CI：1.09-2.72，P=0.020）与较高的 CCyR 率相关。随后的敏感性分析证实了 CYP3A5 rs776746 在亚洲 CML 患者中的统计学意义（显性模型 OR：3.90；95%CI：2.47-6.14，P<0.001；等位基因模型 OR：2.08；95%CI：1.47-2.95，P<0.001）。总之，本荟萃分析支持 SLC22A1 和 CYP3A5 基因型与 CML 患者伊马替尼临床反应率之间的相关性，但仍需要进一步的大型研究，特别是在白种人中，以提供确凿的证据。
