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首页> 外文期刊>International Journal of Clinical and Experimental Medicine >Association of SLCO1B1 gene polymorphisms with toxicity response of high dose methotrexate chemotherapy in childhood acute lymphoblastic leukemia
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Association of SLCO1B1 gene polymorphisms with toxicity response of high dose methotrexate chemotherapy in childhood acute lymphoblastic leukemia

机译：SLCO1B1基因多态性与大剂量氨甲蝶呤化疗对儿童急性淋巴细胞白血病的毒性反应的关系

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Objective: The present study aims to investigate the correlation of polymorphisms of SLCO1B1 gene with the toxicity during therapy with the high-dose methotrexate (MTX) chemotherapy in childhood acute lymphoblastic leukemia. Methods: We analyzed 2 polymorphisms (rs4149081 and rs11045897) in SLCO1B1 gene in 280 Chinese pediatric B-ALL patients, using MTX plasma concentration as an objective and quantifiable marker of toxicity. We utilized Enzyme-multiplied immunoassay technique (EMIT) to measure the plasma concentration of MTX. The polymerase chain reaction-allele specific (PCR-AS) method was utilized to perform the genotyping. Results: We found there was a statistically significant association between MTX plasma concentration and the SLCO1B1 rs11045879 CC genotype (P<0.05). We also found the rs4149081 AA genotype was associated with high-MTX plasma concentrations. A-C haplotype carriers have a higher risk for MTX delayed clearance but G-T haplotype was associated with a lower risk for MTX delayed clearance. Conclusions: The rs4149081 AA genotype and the rs11045897 CC genotype could be indicators for high-MTX plasma concentrations in children with ALL.
机译：目的：本研究旨在探讨SLCO1B1基因多态性与大剂量甲氨蝶呤（MTX）化疗治疗儿童急性淋巴细胞白血病的毒性之间的相关性。方法：我们以MTX血浆浓度作为客观和定量的毒性指标，分析了280例中国小儿B-ALL患者SLCO1B1基因的2个多态性（rs4149081和rs11045897）。我们利用酶促免疫测定技术（EMIT）来测量MTX的血浆浓度。利用聚合酶链反应-等位基因特异性（PCR-AS）方法进行基因分型。结果：我们发现MTX血浆浓度与SLCO1B1 rs11045879 CC基因型之间存在统计学上的显着相关性（P＆＃x0003c; 0.05）。我们还发现rs4149081 AA基因型与高MTX血浆浓度相关。 A-C单倍型携带者MTX延迟清除的风险较高，而G-T单倍型携带MTX延迟清除的风险较低。结论：rs4149081 AA基因型和rs11045897 CC基因型可能是ALL患儿高MTX血浆浓度的指标。

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