奥氮平致体质量增加与HTR2C受体基因-759C/T多态性的关联研究  

Study of the Association Between Olanzapine-induced Weight Gain and the-759C/T Polymorphism of HTR2C Receptor Gene

作　　者：刘伟忠[1] 何红波[1] 何震宇[2] 黄惜妮[1] 张敏玲[1] 张杰[2] 梅尚英[1] 刘文宪[1] 

机构地区：[1]广州市脑科医院国家药品临床试验机构,广州510370 [2]广东药学院生物化学与分子生物学系,广州510006

出　　处：《医药导报》2013年第6期733-737,共5页Herald of Medicine

基　　金：广东省科技计划立项资助项目(2010B031600180)

摘　　要：目的探讨奥氮平在治疗精神分裂症患者过程中出现的体质量增加与5-羟色胺2C(HTR2C)受体基因启动子区-759C/T(rs3813929)单核苷酸多态性的关系。方法选择首发精神分裂症患者181例,测定其接受奥氮平单药治疗前及治疗12周后的体质量、血糖、三酰甘油、胆固醇指标,计算体质量指数(BMI),采用聚合酶链反应-限制性片段长度多态(PCR-RFLP)技术检测各患者HTR2C受体基因-759C/T位点的半合子型或基因型,分析BMI的变化与-759C/T的相关性。结果 181例患者经奥氮平治疗后平均体质量增加(4.33±4.15)kg或超过基础体质量的(7.1±6.3)%,体质量变化范围为0～22 kg或0%～38%,平均BMI变化值为(1.52±1.48)kg.(m2)-1。92例男患者突变型半合子(-759T)频率为13.0%,89例女患者突变型纯合子(-759T/T)频率为0%,杂合子频率(-759C/T)为29.2%。-759C/C野生型纯合子女患者和-759C半合子男患者经奥氮平治疗后体质量增加更明显。结论 HTR2C受体基因启动子-759C/T单核苷酸多态性与奥氮平治疗导致患者体质量增加相关联,携带-759T等位基因可能是限制体质量增加的保护因子。Objective To study the association between single nucleotide polymorphism of 5-hydroxytryptamine 2C （HTR2C） receptor gene-759C/T （rs3813929） and weight gain in patients with schizophrenia treated with olanzapine. Methods Monotherapy with olanzapine was given to 181 first-episode schizophrenia patients （92 males, 89 females） for 12 weeks. The body weight, serum levels of glucose, triglyceride and cholesterol were measured before and after the therapy, and body mass index （BMI） was calculated. PCR-RFLP was used to analyze the frequencies of HTR2C receptor gene-759C/T hemizygote and genotype. The correlation between hemizygote or genotype and the changes of BMI value was analyzed. Results There was an average increase in body weigh of （4.33±4.15） kg, or （7.1±6.3）% from the baseline with a range of 0-22 kg or 0%-38%. The average BMI value was increased by （1.52± 1.48） kg ·（m2） -1 The frequency of mutant homozygote was 13.0% among the 92 male patients. The frequency of mutant homozygote and the mutant heterozygote was 0% and 29.2%, respectively, among the 89 female patients. The patients with-759C/C wild type homozygote （female） and -759C hemizygote （male） had more weight gain after olanzapine treatment . Conclusion The HTR2C receptor gene-759C/T polymorphism might be associated with olanzapine-induced weight gain, and -759T potentially could be a protective factor to prevent excessive weight gain in schizophrenia patients treated with olanzapine.

关 键 词：奥氮平 体质量增加 5-羟色胺 基因多态性 

分 类 号：R971.4[医药卫生—药品] R969[医药卫生—药学]