Dopamine D3-receptor gene variant and susceptibility to tardive dyskinesia in schizophrenic patients
Dopamine D3-receptor gene variant and susceptibility to tardive dyskinesia in schizophrenic patients
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DOI：
10.1038/sj.mp.4000249
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发表时间：
1997-03-01
影响因子：
11
通讯作者：
McCreadie, RG
中科院分区：
文献类型：
--
作者：
Steen, VM;Lovlie, R;McCreadie, RG
精神分裂症是一种严重的精神疾病，其终生风险约为1%。许多患者（但不是全部）受益于已知阻断多巴胺D2样受体的抗精神病药物的治疗。然而，常规精神抑制剂的使用受到锥体外系副作用风险的阻碍，迟发性运动障碍（TD）由于其高患病率和潜在的不可逆性质而通常被认为是这些药物引起的运动障碍中最严重的。我们研究了多巴胺D3受体基因（DRD 3）的遗传变异作为接受长期抗精神病药物治疗的精神分裂症患者中TD的假定危险因素，我们发现高频率（22-24%）的纯合性的Ser 9 Gly变异在横向和纵向评估中，Tn受试者中DRD 3基因的等位基因2，与无TD或TD波动患者中该基因型的相对低代表性（4-6%）相比，该结果表明两个多态性Ser 9 Gly等位基因的常染色体遗传（2-2基因型），但不是野生型等位基因的纯合性（1-1基因型），是TD发展的易感因素，这一观察结果可能会提高对TD病理生理机制的理解，并影响未来抗精神病药物的设计和选择，严重的运动副作用和遗传标记之间的相关性可能会导致选择偏差的精神分裂症患者的遗传研究的采样，因此可以解释精神分裂症本身的易感性和纯合性的DRD 3基因之间的明显关联。
Schizophrenia is a serious psychiatric illness with a life-time risk of approximately one percent, Many of the patients, but not all, benefit from treatment with anti-psychotic drugs known to block dopamine D2-like receptors, The use of conventional neuroleptics is, however, hampered by the risk of extrapyramidal side-effects, Tardive dyskinesia (TD) is usually regarded as the most serious of these drug-induced movement disorders due to its high prevalence and potentially irreversible nature, In this study, we have investigated the genetic variation of the dopamine D3 receptor gene (DRD3) as a putative risk factor for TD in schizophrenic patients receiving long-term anti-psychotic drug therapy, We found a high frequency (22-24%) of homozygosity for the Ser9Gly variant (allele 2) of the DRD3 gene among subjects with Tn in both a cross-sectional and a longitudinal evaluation, as compared with the relative underrepresentation (4-6%) of this genotype in patients with no or fluctuating TD, This result indicates that autosomal inheritance of two polymorphic Ser9Gly alleles (2-2 genotype), but not homozygosity for the wild-type allele (1-1 genotype), is a susceptibility factor for the development of TD an observation which may improve the understanding of the pathophysiological mechanisms of TD and influence the design and choice of future anti-psychotic drugs, The correlation between a serious motor side-effect and a genetic marker could lead to selection bias in the sampling of schizophrenic patients for genetic studies, and may therefore explain the apparent association reported between susceptibility for schizophrenia per se and homozygosity for the DRD3 gene.