CYP1A2基因C734A多态性和奥氮平临床效应的关联研究

目的探讨细胞色素P450(CYP)1A2酶基因C734A多态性和奥氮平临床效应的关系。方法随机选取113例精神分裂症患者给予奥氮平足量治疗8周,治疗前后以阳性和阴性症状量表(PANSS)评定疗效,测定治疗前后的血糖、血脂和体重,采用聚合酶链式反应-限制性片断长度多态性(PCR-RFLP)技术检测患者的基因多态性。从3个角度分析C734A多态性与疗效的关系。结果以PANSS减分率50％为界将患者分为有效组(69例)和无效组(44例),两组间CYP1A2基因C734A多态性的基因型和等位基因频率差异无显著性(X2=3．13,P> 0．05;X2=0．48,P>0．05);以基因型不同分组比较,各组间PANSS的总分、阳性症状分、阴性症状分等指标的减分／减分率的差异均无显著性(F值为0．14-1．74,P>0．05);多元线性回归分析结果显示,未发现病程、治疗前PANSS总分、用药剂量等混杂因素对疗效具有明显的影响(P>0．05),而PANSS的总分、阳性症状分、阴性症状分的减分率等疗效指标与CYP1A2基因均不存在线性回归关系(各偏回归系数检验t值分别为-0．52,-0．04, -0．49,P>0．05)。不同基因型组间治疗后的血糖、血脂升高和体重增加的差异也无显著性(F值为0．02-0．89, P>0．05)。结论CYP1A2基因C734A多态性与奥氮平治疗精神分裂症的疗效无关,与其所致的糖脂改变和体重增加也无关联。

Association study of C734A polymorphism of cytochrome P450 1A2 (CYP1A2) gene and clinical response of Olanzapine

Objective To investigate the relationship between C734A polymorphism of CYP1A2 gene and Olanza-pine response in the treatment of schizophrenia. Methods 113 patients with schizophrenia were received 8-week Olanzapine treatment. Efficacy was evaluated by the Positive and Negative Syndrome Scale, and biochemical measures were collected at baseline and at the end of the 8-week. Genotypes were analyzed by PCR-RFLP techniques. Results Patients were divided into responder group (69) and non-responder group (44) by threshold of 50% baseline-endpoint decrease rate in PANSS score, frequencies of genotype and alleles of C734A polymorphism of CYP1A2 gene were not significantly different between the two groups. While no significant differences in decreases or decrease rates in PANSS score, positive symptom score and negative symptom score were found between different genotype groups. A multiple linear regression analysis showed genotype of CYP1A2 gene had not significant effect on decrease rates in PANSS score, positive symptom score or negative symptom score. In addition, confounding effects of duration of illness, initial PANSS score and dose on change in above clinical response indexes could not be detected. Differences of increases after treatment in glucose, triglyceride, cholesterol and weight were not significant between genotype groups. Conclusions CYP1A2 gene was not associated with response to Olanzapine treatment and its induced-change in glucose, three-glycerol, cholesterol and weight.