细胞色素P450酶1A2基因多态性与奥氮平临床疗效的相关性分析

Association analysis of cytochrome P450 enzyme 1A2 gene polymorphisms on clinical efficacy of olanzapine

目的探讨rs2470890、rs2069521基因多态性与奥氮平临床疗效之间的关系。方法精神分裂症患者104例,给予奥氮平5~20 mg·d^-1治疗6周,通过阳性和阴性症状量表(PANSS)来评估奥氮平治疗精神分裂症的疗效,按照PANSS减分率≥50%和<50%分为有效组和无效组。采用Sequenom MassArray系统基因分型方法检测CYP1A2(rs2470890)、CYP1A2(rs2069521)基因多态性;比较治疗前后患者的体重、谷丙转氨酶(ALT)、谷草转氨酶(AST)、尿素(Urea)、尿酸(UA)、总胆固醇(T-CHO)、甘油三酯(TG)、血糖(GLU)、泌乳素(PRL)的变化。结果服药后患者体重、ALT、AST、TG、PRL均有显著性增加(P<0.05),GLU没有显著变化(P>0.05);CYP1A2(rs2470890)基因中TT型与TC+CC型对奥氮平临床疗效无显著性差异(OR=1.588,95%CI:0.53~4.75,P>0.05);CYP1A2(rs2069521)基因中GG型与GA+AA型对奥氮平临床疗效无显著性差异(OR=0.51,95%CI:0.14~1.90,P>0.05)。结论奥氮平会导致患者体重增加,ALT、AST、TG、PRL水平升高,奥氮平临床疗效与CYP1A2(rs2470890)、CYP1A2(rs2069521)基因多态性无关。

Objective To investigate the relationship between rs2470890 and rs2069521 gene polymorphisms and clinical efficacy of olanzapine.Methods 104 patients with schizophrenia were treated with olanzapine 5-20 mg·d^-1 for 6 weeks.The positive and negative symptom scale(PANSS)was used to evaluate the efficacy of olanzapine in the treatment of schizophrenia.PANSS reduction rate≥50%and<50%are divided into effective group and ineffective group.The Sequenom MassArray genotyping method was used to detect CYP1A2(rs2470890)and CYP1A2(rs2069521)gene polymorphisms.The body weight,alanine aminotransferase(ALT),aspartate aminotransferase(AST),Urea,uric acid(UA),total cholesterol(T-CHO),triglycerides(TG),blood glucose(GLU),and prolactin(PRL)were compared before and after treatment.Results Patients’weight,ALT,AST,TG,and PRL all increased significantly after taking the drug(P<0.05),and there was no significant change in GLU(P>0.05).The clinical effect of TT and TC+CC in CYP1 A2(rs2470890)gene on olanzapine had no significant difference(OR=1.588,95%CI:0.53~4.75,P>0.05);GG type and GA+AA type in CYP1A2(rs2069521)gene had no significant difference in clinical efficacy of olanzapine(OR=0.51,95%CI:0.14~1.90,P>0.05).Conclusion Olanzapine can lead to weight gain,elevated levels of ALT,AST,TG and PRL.The clinical efficacy of olanzapine is not related to CYP1A2(rs2470890)and CYP1A2(rs2069521)gene polymorphisms.