Effects of Glycogen Synthase Kinase-3 Beta Gene Polymorphisms on the Plasma Concentration of Aripiprazole in Chinese Patients with Schizophrenia: A Preliminary Study

• Published in: Journal of molecular neuroscience Vol. 73; no. 1; pp. 76 - 83
• Main Authors: Xu, Zhizhong, Wen, Chunyan, Huang, Yinghua, Yuan, Qianfa, Zhang, Xianhua, Lin, Duoduo, Liu, Liangsheng, Wang, Wenqiang
• Format: Journal Article
• Language: English
• Published: New York Springer US 2023; Springer Nature B.V
• Subjects: Antipsychotics; Aripiprazole; Aripiprazole - therapeutic use; Biomedical and Life Sciences; Biomedicine; Cell Biology; East Asian People; Gene Frequency; Gene polymorphism; Genotype; Genotypes; Glycogen; Glycogen synthase kinase 3; Glycogen Synthase Kinase 3 beta - genetics; Glycogens; Haplotypes; High performance liquid chromatography; Humans; Kinases; Linkage analysis; Linkage Disequilibrium; Liquid chromatography; Mass spectrometry; Mass spectroscopy; Mental disorders; Neurochemistry; Neurology; Neurosciences; Nucleotides; Plasma; Polymerase chain reaction; Polymorphism; Polymorphism, Single Nucleotide; Proteomics; Schizophrenia; Schizophrenia - drug therapy; Schizophrenia - genetics; Single-nucleotide polymorphism; Single-nucleotide polymorphisms; High-performance liquid chromatography-mass spectrometer; Antipsychotic agent; Genotype distribution; Linkage disequilibrium analysis
• ISSN: 0895-8696; 1559-1166
• DOI: 10.1007/s12031-022-02079-7

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.