Effect of CYP1A2 gene polymorphism on plasma concentration of olanzapine in schizophrenic patients

Objective To investigate the effect of cytochrome P450 1 A2(CYP1 A2) gene polymorphism on plasma concentration of olanzapine in schizophrenic patients, and to provide reference for the individualized administration of olanzapine. Methods A total of 226 schizophrenic patients treated with olanzapine in Hangzhou Seventh People's Hospital from June 2017 to December 2018 were selected as subjects in the study. The plasma concentration of olanzapine was determined by ultra-high-performance liquid chromatography-tandem mass spectrometry. The gene polymorphisms of CYP1 A2*1 C and CYP1 A2*1 F were detected by improved multiple ligase detection reaction, and the CYP1 A2 genotypes were classified into high activity genotype(HA) and low activity genotype(LA) based on these two gene polymorphism sites. Then the difference in plasma concentration of olanzapine among different genotypes were compared. Results The plasma concentrations of olanzapine in the genotypes of GG/AA, GG/CA and GA/AA were obviously lower than that in the wild GG/CC genotype [(2.17±0.79)ng/(mL·mg),(2.53±1.10)ng/(mL·mg),(2.44±0.79)ng/(mL·mg) vs.(2.99±1.00)ng/(mL·mg),F=3.312,P<0.05]. However, there was no significant difference in the genotypes of GG/CC,GA/CA and AA/AA or in the genotypes of GG/AA,GG/CA and GA/AA(P>0.05).The plasma concentration of olanzapine in high activity genotype was obviously lower than that in low activity genotype [(2.43±0.96)ng/(mL·mg) vs.(2.91±1.06)ng/(mL·mg),t=3.561,P<0.05], and the activity of CYP1 A2 was negatively correlated with the plasma concentration of olanzapine(r=-0.232, P<0.05). Conclusion CYP1 A2 gene polymorphism could affect the plasma concentration of olanzapine. The CYP1 A2 genotypes of GG/AA, GG/CA and GA/AA had low plasma concentrations of olanzapine, and clinicians should pay appropriate attention to it when using olanzapine.