Blood Bank, Faculty of Medicine of Sfax, University of Sfax, Sfax, Tunisia.
Department of Medical Genetic, Faculty of Medicine of Sfax, University of Sfax, Sfax, Tunisia.
J Oncol Pharm Pract. 2022 Jan;28(1):39-48. doi: 10.1177/1078155220981150. Epub 2021 Feb 10.
Our study aimed to investigate the association between multidrug resistance (MDR1) C1236T, C3435T and G2677T/A polymorphisms and the response to imatinib (IM) in chronic myeloid leukemia (CML).
An electronic databases in PubMed, Embase, Web of Knowledge, Scopus and Cochrane were searched using combinations of keywords relating to MDR1 polymorphisms and the response to IM in CML. Studies retrieved from database searches were screened using strict inclusion and exclusion criteria.
In total, 37 studies were initially identified, and 17 studies, involving 4494 CML patients, were eventually included in this meta-analysis.Results of our study revealed significant association between MDR1 G2677T/A and C3435T polymorphisms and response to IM in Caucasian population under recessive model (T or A vs G; OR = 1.43,95%CI [1;06-1.93]; T vs C;OR = 1.13; 95%IC [0.79; 1.63]), dominant (T or A vs G; OR = 0.94; 95%CI [0.74-1.21]; T vs C; OR = 1.49; 95%CI [1.02-2.17]) and heterozygous models (T or A vs G; OR = 0.83; 95%CI [0.64; 1.09]; T vs C; OR = 1.52; 95%CI [1.01-2.28]); respectively. However, never significative association was found between IM response and the MDR1 C1236T polymorphism (OR = 1.25; 95%CI [0.46; 3.33]).
The MDR1 G2677T/A and C3435T polymorphisms might be a risk factor for resistance to IM in Caucasian CML patients.
本研究旨在探讨多药耐药基因(MDR1)C1236T、C3435T 和 G2677T/A 多态性与伊马替尼(IM)治疗慢性髓系白血病(CML)反应之间的关系。
在 PubMed、Embase、Web of Knowledge、Scopus 和 Cochrane 电子数据库中,使用与 MDR1 多态性和 CML 中 IM 反应相关的关键词组合进行了搜索。从数据库检索中筛选出符合严格纳入和排除标准的研究。
共初检到 37 项研究,最终纳入了 17 项研究,共计 4494 例 CML 患者。我们的研究结果表明,在白种人群中,MDR1 G2677T/A 和 C3435T 多态性与 IM 反应之间存在显著相关性,在隐性模型下(T 或 A 与 G 相比;OR=1.43,95%CI [1;06-1.93];T 与 C 相比;OR=1.13;95%CI [0.79;1.63])、显性模型(T 或 A 与 G 相比;OR=0.94;95%CI [0.74-1.21];T 与 C 相比;OR=1.49;95%CI [1.02-2.17])和杂合模型(T 或 A 与 G 相比;OR=0.83;95%CI [0.64;1.09];T 与 C 相比;OR=1.52;95%CI [1.01-2.28])。然而,IM 反应与 MDR1 C1236T 多态性之间从未发现显著相关性(OR=1.25;95%CI [0.46;3.33])。
MDR1 G2677T/A 和 C3435T 多态性可能是白种人 CML 患者对 IM 耐药的危险因素。