糖原合成酶激酶-3 β基因多态性对中国精神分裂症患者阿立哌唑血药浓度影响的初步研究

IF 2.8 4区 医学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Journal of Molecular Neuroscience Pub Date : 2022-12-21 DOI:10.1007/s12031-022-02079-7
Zhizhong Xu, Chunyan Wen, Yinghua Huang, Qianfa Yuan, Xianhua Zhang, Duoduo Lin, Liangsheng Liu, Wenqiang Wang
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摘要

本研究探讨了精神分裂症患者与健康对照者糖原合成酶激酶3β (GSK3β)基因多态性的差异,并探讨了基因多态性与阿立哌唑血药浓度的关系。我们从闽南招募了127名精神分裂症患者和125名健康对照。采用扩增聚合酶链反应测定GSK3β rs6438552、rs12630592和rs3732361位点的基因型,采用高效液相色谱-串联质谱法测定阿立哌唑的血药浓度。GSK3β的3个基因座各有3个基因型。各基因座的基因型分布差异不显著,但各基因座内的等位基因频率在精神分裂症组和对照组之间存在显著差异。对三个单核苷酸多态性(snp)的连锁不平衡分析显示了强连锁。单倍型分析结果显示,GSK3β的3个snp中存在2个单倍型。阿立哌唑的血药浓度、剂量校正浓度和归一化浓度在三个snp的不同基因型之间存在显著差异。综上所述,GSK3β基因位点rs6438552、rs12630592和rs3732361可能与精神分裂症有关,且GSK3β基因多态性可能与阿立哌唑血药浓度相关。
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Effects of Glycogen Synthase Kinase-3 Beta Gene Polymorphisms on the Plasma Concentration of Aripiprazole in Chinese Patients with Schizophrenia: A Preliminary Study

This study explored the differences in glycogen synthase kinase-3 beta (GSK3β) gene polymorphisms between patients with schizophrenia and healthy controls and investigated the association between gene polymorphisms and plasma concentration of aripiprazole. We enrolled 127 patients with schizophrenia and 125 healthy controls from southern Fujian. The genotypes of the rs6438552, rs12630592, and rs3732361 loci of GSK3β were evaluated by sequencing with amplified polymerase chain reaction, and the plasma concentration of aripiprazole was determined by high-performance liquid chromatography-tandem mass spectrometry. All three loci of GSK3β had three genotypes each. The genotype distribution in each locus was not significantly different, but there was a significant difference in the allele frequency between the schizophrenia and control groups within each locus. Linkage disequilibrium analyses of the three single-nucleotide polymorphisms (SNPs) revealed strong linkage. The haplotype analysis results showed two haplotypes in the three SNPs of GSK3β. The plasma concentrations, dose-corrected concentrations, and normalized concentrations of aripiprazole were significantly different among the different genotypes of the three SNPs. In conclusion, the rs6438552, rs12630592, and rs3732361 loci of GSK3β may be involved in schizophrenia, and GSK3β gene polymorphism may be correlated with the plasma concentration of aripiprazole.

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来源期刊
Journal of Molecular Neuroscience
Journal of Molecular Neuroscience 医学-神经科学
CiteScore
6.60
自引率
3.20%
发文量
142
审稿时长
1 months
期刊介绍: The Journal of Molecular Neuroscience is committed to the rapid publication of original findings that increase our understanding of the molecular structure, function, and development of the nervous system. The criteria for acceptance of manuscripts will be scientific excellence, originality, and relevance to the field of molecular neuroscience. Manuscripts with clinical relevance are especially encouraged since the journal seeks to provide a means for accelerating the progression of basic research findings toward clinical utilization. All experiments described in the Journal of Molecular Neuroscience that involve the use of animal or human subjects must have been approved by the appropriate institutional review committee and conform to accepted ethical standards.
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