Megías-Vericat J E, Rojas L, Herrero M J, Bosó V, Montesinos P, Moscardó F, Poveda J L, Sanz M Á, Aliño S F
1] Unidad de Farmacogenética, Instituto Investigación Sanitaria La Fe and Área del Medicamento Hospital Universitario y Politécnico La Fe. Av. Fernando Abril Martorell, Valencia, Spain [2] Servicio de Farmacia, Área del Medicamento, Hospital Universitario y Politécnico La Fe. Av. Fernando Abril Martorell, Valencia, Spain.
1] Unidad de Farmacogenética, Instituto Investigación Sanitaria La Fe and Área del Medicamento Hospital Universitario y Politécnico La Fe. Av. Fernando Abril Martorell, Valencia, Spain [2] Department of Internal Medicine, Faculty of Medicine, Pontificia Universidad Católica de Chile, Av. Libertador Bernardo O Higgins, Santiago, Chile.
Pharmacogenomics J. 2015 Apr;15(2):109-18. doi: 10.1038/tpj.2014.80. Epub 2015 Jan 6.
The ABCB1 gene encodes for P-glycoprotein (P-gp), an efflux pump for a variety of xenobiotics. The role of ABCB1 polymorphisms in acute myeloid leukemia (AML) outcomes of standard chemotherapy (cytarabine plus anthracyclines) remains controversial. A systematic search was made of studies evaluating the association between ABCB1 polymorphisms 1236C>T, 2677G>T/A and 3435C>T and effectiveness variables. We found seven cohort studies (1241 patients) showing a significantly higher overall survival (OS) among carriers of the variant allele of 1236C>T at year 4 (odds ratio (OR): 1.47, 95% confidence interval (CI): 1.07-2.01), 2677G>T/A at years 4-5 (OR: 1.37, 95% CI: 1.01-1.86) and 3435C>T at years 3 (OR: 1.41, 95% CI: 1.03-1.94) and 4-5 (OR: 1.42, 95% CI: 1.05-1.91). In the subgroup analysis according to ethnicity, Caucasians carrying variant allele showed consistent results in OS. ABCB1 influence upon complete remission could not be demonstrated. Future studies based on larger populations and multiethnic groups should help clarify the effect of P-gp polymorphisms upon other outcomes.
ABCB1基因编码P-糖蛋白（P-gp），这是一种针对多种外源性物质的外排泵。ABCB1基因多态性在标准化疗（阿糖胞苷加蒽环类药物）治疗急性髓系白血病（AML）的疗效方面的作用仍存在争议。我们系统检索了评估ABCB1基因多态性1236C>T、2677G>T/A和3435C>T与疗效变量之间关联的研究。我们发现七项队列研究（1241例患者）显示，在第4年时，1236C>T变异等位基因携带者的总生存期（OS）显著更高（优势比（OR）：1.47，95%置信区间（CI）：1.07 - 2.01）；在第4至5年时，2677G>T/A变异等位基因携带者的OS显著更高（OR：1.37，95% CI：1.01 - 1.86）；在第3年时，3435C>T变异等位基因携带者的OS显著更高（OR：1.41，95% CI：1.03 - 1.94），在第4至5年时也是如此（OR：1.42，95% CI：1.05 - 1.91）。在按种族进行的亚组分析中，携带变异等位基因的白种人在OS方面呈现出一致的结果。未证实ABCB1对完全缓解有影响。基于更大样本量人群和多民族群体的未来研究应有助于阐明P-糖蛋白多态性对其他结局的影响。
