种代号为ABCB1的多态性在和CYP19A1基因影响阿那曲唑血浆浓度和绝经后乳腺癌患者的临床结果。
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Gervasini G, hara C, C脂肪,罗梅罗N,马丁内斯R, Carrillo农协
种代号为ABCB1的多态性在和CYP19A1基因影响阿那曲唑血浆浓度和绝经后乳腺癌患者的临床结果。
Br中国新药杂志。2017年3月,83 (3):562 - 571。doi: 10.1111 / bcp.13130。Epub 2016年10月18日。
- PubMed ID
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27747906 (在PubMed]
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目的:阿那曲唑,芳香化酶抑制剂广泛用于乳腺癌、最近表示22种代号为ABCB1的()衬底。我们种代号为ABCB1的旨在确定单核苷酸多态性(snp)会影响阿那曲唑血浆浓度在这些病人。此外,我们评估了单核苷酸多态性的影响在CYP19A1和TCL1A关节痛和癌症复发的发展在我们的系列。方法:本研究包括110名绝经后激素受体阳性乳腺癌的女性。阿那曲唑血浆水平取决于液体chromatography-electrospray ionization-quadrupole-time-of-flight质谱分析系统。种代号为ABCB1的患者的snp基因分型,TCL1A和CYP19A1基因搜索关联与药代动力学和药效学参数使用逻辑回归模型。必威国际app结果:阿那曲唑浓度显示近9倍个人间变异性(平均26.95 + / - 11.91 ng毫升(1))。种代号为ABCB1的的2677 - tt基因型与等离子体水平较高(32.22 + / - 12.82和25.86 + / - 11.56 ng毫升(1)GG / GT科目;95%置信区间:-12.3 - -0.40),而3435 - tt基因型显示关节痛的风险保护作用(优势比= 0.32 (0.11 - -0.89);P = 0.029)。 The CYP19A1 rs1008805 GG genotype was strongly and inversely associated with arthralgia (odds ratio = 0.24 [0.09-0.65], P = 0.004); however, SNPs near the TCL1A gene were not linked to this adverse effect. None of the patients who had cancer recurrence harboured the CYP19A1 rs727479 AA genotype, which, in contrast, was present in 38% of patients who did not relapse (P for trend = 0.031). CONCLUSION: Our findings indicate that variability in anastrozole plasma levels may be attributable to the status of the ABCB1 gene locus. Furthermore, genetic variants in CYP19A1 were associated with arthralgia and cancer recurrence in our patients.