血液病患者中GSTA1基因多态性分析及其对GST酶活性的影响

doi:10.5246/jcps.2019.06.038

摘要/Abstract

摘要：

谷胱甘肽硫转移酶(GSTs)是体内重要的药物代谢酶, 且存在基因多态性的现象。本研究调查了170例血液病患者的GST酶活性和GSTA1基因多态性, 并探讨了它们之间的关系。通过PCR-RFLP技术分析患者的GSTA1基因多态性, DNA测序仪确定启动子区域中的四个突变位点(-631, -567, -69和-52)的碱基序列; 通过测量CDNB和GSH之间催化反应的速率来计算患者的GST酶活性。结果显示, 男性和女性的平均GST活性分别为5.20±0.13和5.17±0.12 nmol/min/mL, 差异不显著(P=0.91)。基因型GSTA1*A*A、GSTA1*A*B和GSTA1*B*B的频率分别为75.3%, 22.9%和1.8%; 等位基因GSTA1*A和*B频率为86.8%和13.2%。通过卡方检验, 男性和女性之间的基因型频率分布没有显着差异(P = 0.743)。杂合突变基因型的平均GST活性(4.83±0.76 nmol/min/mL)低于野生基因型(5.34±1.26 nmol/min/mL, P = 0.018), 高于纯合突变基因型(3.32±0.07 nmol/min/mL, P = 0.022)。这些发现可能有助于改善血液病患者的个体化治疗, 并促进血液病精准医学的发展。

关键词: 基因多态性, 谷胱甘肽硫转移酶, 血液病, 酶活性, PCR

Abstract:

Glutathione S-transferases (GSTs) are important drug-metabolizing enzymes that catalyze the binding of glutathione (GSH) to electrophilic substances. GST has genetic polymorphism, and the enzyme activity of GST affects the metabolism of certain drugs in vivo. In the present day, we investigated the GST enzyme activity and GSTA1 gene polymorphism in 170 patients with hematological diseases and explored their relationship. The GSTA1 gene polymorphism of the patient was analyzed by PCR- restriction fragment length polymorphism (PCR-RFLP) technique, and the base sequences of the four mutation sites (-631, -567, -69, and -52) in the promoter region were determined by DNA-Sequencer. The patient's GST enzyme activity was calculated by measuring the rate at which it catalyzed the reaction between 1-chloro-2,4-dinitrobenzene (CDNB) and GSH. The average GST enzyme activities of males and females were 5.20±0.13 and 5.17±0.12 nmol/min/mL, respectively, and the difference was not significant (P = 0.91). The frequencies of genotypes GSTA1*A*A (wild genotype), GSTA1*A*B (heterozygous genotype), and GSTA1*B*B (homozygous mutant genotype) were 75.3%, 22.9%, and 1.8%, respectively. Alleles GSTA1*A and *B were distributed at 86.8% and 13.2%, respectively. The genotype frequency distribution between males and females was no significant difference by Pearson’s chi-square test (P = 0.743). The average GST activity of the heterozygous mutant genotype (4.83±0.76 nmol/min/mL) was lower than the wild genotype (5.34±1.26 nmol/min/mL, P = 0.018), and higher than that of the homozygous mutant genotype (3.32±0.07 nmol/min/mL, P = 0.022). These findings might help us improve the individualized treatment of patients with hematological diseases in the future and promote the development of precision medicine for blood diseases.

Key words: Polymorphism, Glutathione S-transferase, Hematological disease, Enzyme activity, PCR

中图分类号:

R968

Supporting:

喻光燚, 杨青山, 张国顺, 谢茵, 张丽锋. 血液病患者中GSTA1基因多态性分析及其对GST酶活性的影响[J]. 中国药学(英文版), 2019, 28(6): 393-401.

Guangyi Yu, Qingshan Yang, Guoshun Zhang, Yin Xie, Lifeng Zhang. Polymorphism analysis of Glutathione S-transferase A1 in patients with hematological diseases and its effect on GST enzyme activity[J]. Journal of Chinese Pharmaceutical Sciences, 2019, 28(6): 393-401.

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