上海交通大学学报（医学版）

上海交通大学学报（医学版）

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DRD2、HTR2A和HTR2C基因在氯氮平诱导代谢综合征发生中的作用

张 毅1，张 晨1,2，陈美娟1，袁爱花1，禹顺英1，方贻儒1   

  1. 1.上海交通大学 医学院附属精神卫生中心心境障碍科， 上海 200030； 2.中国科学院昆明动物研究所动物模型与人类疾病机理重点实验室， 昆明 650223
  • 出版日期:2014-04-28 发布日期:2014-05-13
  • 通讯作者: 张 晨, 电子信箱: zhangchen645@gmail.com; 方贻儒, 电子信箱: yirufang@aliyun.com。
  • 作者简介:张 毅（1970—）， 男， 副主任医师， 学士; 电子信箱: jeanzy@163.com。
  • 基金资助:

    国家自然科学基金（91232719，81000581）；“十二五”国家科技支撑项目（2012BAI01B04）；上海市科学技术发展基金（12140904200）；中国博士后基金（2013M530410）；国家临床重点专科-上海市精神卫生中心（卫生部医政司2011-873）

Effects of DRD2, HTR2A, and HTR2C genes on process of metabolic syndrome induced by clozapine

ZHANG Yi1, ZHANG Chen1,2, CHEN Mei-juan1, YUAN Ai-hua1, YU Shun-ying1, FANG Yi-ru1   

  1. 1.Division of Mood Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China; 2.Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Kunming 650223, China
  • Online:2014-04-28 Published:2014-05-13
  • Supported by:

    National Natural Science Foundation of China, 91232719,81000581; the “12th Five-year Plan” of National Key Technologies R&D Program, 2012BAI01B04; Shanghai Science & Technology Development Foundation, 12140904200; China Postdoctoral Science Foundation, 2013M530410; National Key Clinical Disciplines at Shanghai Mental Health Center, OMA-MH, 2011-873

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摘要：

目的 探讨多巴胺D2受体（DRD2）、5-羟色胺2A受体（HTR2A）及5-羟色胺2C受体（HTR2C）基因在氯氮平诱导代谢综合征（MS）发生过程中的作用。方法 根据美国国家胆固醇教育项目成人治疗组第三次指南（NCEP-ATPⅢ）的诊断标准，将199例长期服用氯氮平的精神分裂症患者分为MS组和非MS组，选取DRD2、HTR2A及HTR2C功能单核苷酸多态性（SNP）位点rs1800497、rs6311和rs1414334，采用SNaPshot SNP基因分型技术对所有患者进行检验，并测定患者空腹血糖（FPG）、三酰甘油（TG）、高密度脂蛋白（HDL）等生化指标。结果 两组体质量指数、腰围、FPG、TG、HDL、收缩压及舒张压比较差异均有统计学意义（P<0.05）。两组SNP位点基因型及等位基因频率分布的差异无统计学差异（P>0.05）。rs1800497不同基因型携带者FPG比较差异有统计学意义（F=3.4, P=0.036），其中T/T基因型携带者FPG水平显著高于C/T携带者（P=0.011）。结论 DRD2基因rs1800497可能不是氯氮平诱导MS的直接作用位点，但可能通过影响DRD2表达，造成患者体内糖代谢异常，增加MS的发生风险。

关键词: 多巴胺D2受体, 5-羟色胺2A受体, 5-羟色胺2C受体, 氯氮平, 代谢综合征

Abstract:

Objective To investigate the effects of dopamine D2 receptor (DRD2), 5-serotonin 2A receptor (HTR2A), and 5-serotonin 2C receptor (HTR2C) genes on the process of metabolic syndrome (MS) induced by clozapine. Methods According to the diagnostic criteria of National Cholesterol Education Program's Adult Treatment Panel Ⅲ (NCEP-ATPⅢ), 199 schizophrenic patients with long-term use of clozapine were divided into MS group and non-MS group. The polymorphisms of DRD2, HTR2A, and HTR2C (rs1800497, rs6311 and rs1414334, respectively) were genotyped by the SNaPshot SNP and the serum levels of fasting plasma glucose (FPG), triglyceride (TG), and high density lipoprotein cholesterol (HDL) were measured. Results The differences of body mass index, levels of waist circumference, FPG, TG, HDL, and blood pressure of two groups were statistically significant (P＜0.05). The differences of allele and genotype frequencies of SNPs of two groups were not statistically significant (P>0.05). The differences of FPG levels of patients with different genotypes of rs1800497 were statistically significant (F=3.4, P=0.036) and the FPG levels of patients with T/T genotype were significantly higher than those of patients with C/T genotype (P=0.011). Conclusion The rs1800497 of DRD2 may not be the direct-causing polymorphism of clozapine induced MS. But it may affect the expression of DRD2, cause the abnormal glucose metabolism, and then increase the risk for MS.

Key words: dopamine D2 receptor, 5-serotonin 2A receptor, 5-serotonin 2C receptor, clozapine, metabolic syndrome