Zhang Yu-Xin, Ma Yu, Zhang Hao, Zhang Wen-Ping, Yang Xiao-Ying
Int J Clin Pharmacol Ther. 2020 May;58(5):254-260. doi: 10.5414/CP203462.
This study aimed to investigate the influence of single-nucleotide polymorphism in exon 26 (C3435T) of multidrug resistance 1 () transporter gene on the concentration of methotrexate (MTX) in Chinese childhood patients with acute lymphoblastic leukemia (ALL) receiving intravenous (IV) and intrathecal (IT) high-dose methotrexate (HDMTX) chemotherapy.
C3435T polymorphism was investigated in 60 patients with Chinese childhood ALL. The study also compared the ; polymorphism between the patients with Chinese childhood ALL and the published data on Americans, Mexicans, Caucasians, and Thais. The C3435T polymorphism was identified using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and direct sequence analysis. Cerebrospinal fluid (CSF) and plasma concentrations of MTX were measured using high-performance liquid chromatography (HPLC). MTX concentrations were compared according to C3435T genotypes.
The frequencies of C3435T genotype in male and female patients with Chinese childhood ALL were significantly different (p = 0.001). For the frequencies of C3435T genotype in Hui and Han patients with Chinese childhood ALL there was no difference (p = 0.188). The distribution of allele frequencies in patients with Chinese childhood ALL was similar to the published data on Americans, Mexican, Caucasians, and Thais (p > 0.05). The CSF concentrations of MTX were found to be significantly different between the C allele (CC + CT) carriers and TT homozygous group (p = 0.04). The plasma concentrations of MTX had no significant difference between the C allele (CC + CT) carriers and TT homozygous group (p > 0.1).
This study showed that the polymorphism of C3435T influenced the CSF concentration of MTX in patients with Chinese childhood ALL receiving IV and IT HDMTX treatment.
本研究旨在探讨多药耐药1（）转运蛋白基因外显子26（C3435T）中的单核苷酸多态性对接受静脉（IV）和鞘内（IT）高剂量甲氨蝶呤（HDMTX）化疗的中国儿童急性淋巴细胞白血病（ALL）患者中甲氨蝶呤（MTX）浓度的影响。
对60例中国儿童ALL患者进行C3435T多态性研究。该研究还比较了中国儿童ALL患者与已发表的美国人、墨西哥人、白种人和泰国人的多态性数据。采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）和直接序列分析鉴定C3435T多态性。使用高效液相色谱（HPLC）测量脑脊液（CSF）和血浆中MTX的浓度。根据C3435T基因型比较MTX浓度。
中国儿童ALL男性和女性患者中C3435T基因型频率存在显著差异（p = 0.001）。中国儿童ALL回族和汉族患者中C3435T基因型频率无差异（p = 0.188）。中国儿童ALL患者的等位基因频率分布与已发表的美国人、墨西哥人、白种人和泰国人的数据相似（p > 0.05）。发现C等位基因（CC + CT）携带者与TT纯合组之间的CSF中MTX浓度存在显著差异（p = 0.04）。C等位基因（CC + CT）携带者与TT纯合组之间的血浆中MTX浓度无显著差异（p > 0.1）。
本研究表明，C3435T多态性影响接受IV和IT HDMTX治疗的中国儿童ALL患者CSF中MTX的浓度。
