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目的探讨在舒尼替尼药效学和药代学途径上ABCG2、FLT3、VEGFR2基因多态性与舒尼替尼治疗后血小板减少之间的相关性。方法 82例接受舒尼替尼单药治疗的晚期肾透明细胞癌患者,治疗前进行ABCG2(rs2231137、rs2231142),FLT3(rs1933437)和VEGFR2(rs2305948)基因多态性检测,记录患者治疗后血小板减少程度,评价基因多态性与血小板减少之间的相关性。结果 rs2231137、rs2231142、rs1933437和rs2305948基因型分布符合Hardy-Weinberg遗传平衡定律。rs2231142的CC基因型和AA/AC基因型3、4级血小板减少分别为25.0%和47.6%,两组血小板减少程度有显著差异(χ2=4.518,P=0.034)。rs1933437的TT基因型和CC/CT基因型3、4级血小板减少分别为48.7%和25.6%,两组血小板减少程度有显著差异(χ2=4.719,P=0.030)。rs2231137或rs2305948不同基因型之间的血小板减少程度无显著差异(P>0.05)。结论中国晚期肾透明细胞癌人群应用舒尼替尼治疗后,rs2231142的CC基因型患者比AA/AC基因型患者发生血小板减少的可能性更小,而rs1933437的TT基因型患者比CC/CT基因型患者发生血小板减少可能性更大,测定基因型有利于选择合适的舒尼替尼治疗人群,为个体化治疗提供了依据。
OBJECTIVE: To investigate the relationship between ABCG2, FLT3 and VEGFR2 gene polymorphisms in sunitinib and pharmacokinetics of sunitinib and the thrombocytopenia after sunitinib treatment. Methods Eighty-two patients with advanced renal clear cell carcinoma who underwent sunitinib monotherapy were enrolled in this study. The gene polymorphisms of ABCG2 (rs2231137, rs2231142), FLT3 (rs1933437) and VEGFR2 (rs2305948) were detected before treatment and the thrombocytopenia The degree of evaluation of gene polymorphism and thrombocytopenia correlation. Results The distribution of rs2231137, rs2231142, rs1933437 and rs2305948 genotypes conformed to the Hardy-Weinberg law of genetic balance. The CC genotype of rs2231142 and grade 3 and 4 of AA / AC genotypes were 25.0% and 47.6%, respectively. There was significant difference between the two groups in the degree of thrombocytopenia (χ2 = 4.518, P = 0.034). The TT genotype of rs1933437 and the grade 3 and 4 thrombocytopenia of CC / CT genotype were 48.7% and 25.6%, respectively. There was significant difference between the two groups in the thrombocytopenia (χ2 = 4.719, P = 0.030). There was no significant difference in thrombocytopenia between rs2231137 or rs2305948 genotypes (P> 0.05). Conclusions After treatment with sunitinib in patients with advanced renal clear cell carcinoma in China, patients with CC genotype rs2231142 are less likely to have thrombocytopenia than patients with AA / AC genotype, while those with TT genotype rs1933437 have a lower risk of thrombocytopenia than those with CC / CT genotype Type patients with greater possibility of thrombocytopenia, determination of genotype is conducive to the selection of appropriate sunitinib treatment of the population, provided the basis for individualized treatment.