Zhang Zhijun, Hou Gang, Zhang Xiaobin, Yao Hui, Sha Weiwei, Zhang Xinbao
Department of Psychiatry and Clinical Science Center, Nanjing Brain Hospital, Nanjing Medical University, Nanjing, Jiangsu, 210029 P. R. China. zhijunzhang616@hotmail. com
Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2003 Apr;20(2):98-102.
To further investigate whether the functional polymorphisms of dopamine D2 receptor (DRD2) and dopamine D3 receptor (DRD3) genes associate with the development of tardive dyskinesia (TD) in schizophrenia, and whether the interactive effects of DRD2, DRD3, 5-hydroxytryptamine 2C receptor (HTR2C) and manganese superoxide dismutase (MnSOD) genes contribute to the severity of TD.
The patients with schizophrenia were assessed for TD by the Abnormal Involuntary Movement Scale (AIMS). Eventually, 42 schizophrenics with persistent TD were in the TD group, and 59 schizophrenics without TD were in the non-TD group. The polymorphism of each candidate gene was analyzed using a polymerase chain reaction-based restriction fragment length polymorphism analysis.
The genotype distributions of the candidate genes in the groups were all consistent with the Hardy-Weinberg equilibrium. Allele frequencies for -759C/T and -697G/C polymorphisms in HTR2C gene showed a significant excess of -697 variant (P<0.05) in the patients with TD, compared against those in patients without TD. There were no differences in the distributions of the allelic frequencies and genotypes of Taq I. A polymorphism in DRD2 gene, of Ser/Gly polymorphism in DRD3 gene, and of Ala-9Val polymorphism in MnSOD gene between the TD group and non-TD group (P>0.05). Interestingly, as compared with the other joint allelic types, a significant excess of carrying both DRD3 variant allele (Gly) and MnSOD wild allele (Val) was found in the TD group (P<0.05). However, neither the allele and genotypes nor the clinical demographic characteristics contributed to the higher total AIMS scores in the patients of the TD group. There were no significant differences in any of the clinical demographic characteristics between the subgroups of any genotype in TD and non-TD groups.
The excess of -697 variant in the promoter regulation region of the HTR2C gene may be a risk factor for the susceptibility to the occurrence of TD in Chinese male patients with schizophrenia. A combination of DRD3 variant allele (Gly) and MnSOD wild allele (Val) may increase the susceptibility to the development of TD.
进一步研究多巴胺D2受体（DRD2）基因和多巴胺D3受体（DRD3）基因的功能多态性是否与精神分裂症迟发性运动障碍（TD）的发生相关，以及DRD2、DRD3、5-羟色胺2C受体（HTR2C）和锰超氧化物歧化酶（MnSOD）基因的交互作用是否影响TD的严重程度。
采用异常不自主运动量表（AIMS）对精神分裂症患者进行TD评估。最终，42例持续性TD的精神分裂症患者纳入TD组，59例无TD的精神分裂症患者纳入非TD组。采用聚合酶链反应-限制性片段长度多态性分析方法分析各候选基因的多态性。
各候选基因在两组中的基因型分布均符合Hardy-Weinberg平衡。与非TD患者相比，TD患者中HTR2C基因-759C/T和-697G/C多态性的等位基因频率显示-697变异体显著过量（P<0.05）。TD组和非TD组之间，DRD2基因的Taq I多态性、DRD3基因的Ser/Gly多态性以及MnSOD基因的Ala-9Val多态性在等位基因频率和基因型分布上没有差异（P>0.05）。有趣的是，与其他联合等位基因类型相比，TD组中同时携带DRD3变异等位基因（Gly）和MnSOD野生等位基因（Val）的情况显著过量（P<0.05）。然而，等位基因和基因型以及临床人口统计学特征均未导致TD组患者的AIMS总分更高。TD组和非TD组中任何基因型亚组之间的任何临床人口统计学特征均无显著差异。
HTR2C基因启动子调控区-697变异体过量可能是中国男性精神分裂症患者发生TD易感性的一个危险因素。DRD3变异等位基因（Gly）和MnSOD野生等位基因（Val）的组合可能增加发生TD的易感性。
