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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


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