Susceptibility to neuroleptic-induced tardive dyskinesia and the T102C polymorphism in the serotonin type 2A receptor
Susceptibility to neuroleptic-induced tardive dyskinesia and the T102C polymorphism in the serotonin type 2A receptor
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DOI：
10.1016/s0006-3223(01)01076-9
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发表时间：
2001-07-15
影响因子：
10.6
通讯作者：
Tan, CH
中科院分区：
文献类型：
--
作者：
Tan, EC;Chong, SA;Tan, CH
背景：遗传因素与运动障碍迟发性运动障碍的病理生理有关，可能涉及多巴胺-血清素相互作用。病例对照关联研究已经确定5-HT2A受体基因的T102C多态性与精神分裂症和氯氮平反应性有关。在这项研究中，我们研究了5-HT2A受体基因多态性与长期服用抗精神病药物导致精神分裂症和迟发性运动障碍的风险因素之间的关系。方法：采用PCR-RFLP方法对97例无精神病史的健康对照者和221例精神分裂症患者（其中有迟发性运动障碍者87例，无迟发性运动障碍者134例）进行基因分型。结果：病例与对照组比较，C等位基因与精神分裂症无显著相关性。迟发性运动障碍患者与未发生迟发性运动障碍患者的等位基因频率差异有统计学意义（p = 0.044, OR = 1.54, 95% CI = 1.02-2.33）。即使在调整年龄和抗精神病药剂量后，差异仍然显著（p = 0.041），优势比为1.64 （95% CI 1.02-2.62）。结论：5-HT2A受体的遗传变异可能与精神分裂症患者抗精神病药诱导的迟发性运动障碍有关。需要进一步的研究来重复这一发现。5-HT2A受体在迟发性运动障碍或难治性精神分裂症病因学中的作用有待进一步研究。(C) 2001年生物精神病学学会。
Background: Genetic factors have been implicated in the pathophysiology of the movement disorder tardive dyskinesia, which may involve dopamine-serotonin interaction. Case-control association studies have identified the T102C polymorphism of the 5-HT2A receptor gene as being associated with schizophrenia and responsiveness to clozapine. In this study, we examine the association of this polymorphism in the 5-HT2A receptor gene as a risk factor for developing schizophrenia and tardive dyskinesia from prolonged treatment with neuroleptics.Methods: Ninety-seven healthy control subjects with no history of mental illness and 221 schizophrenic patients (87 with tardive dyskinesia, 134 without) were genotyped by PCR-RFLP.Results: Comparison between cases and control subjects revealed no significant association between the C allele and schizophrenia. There was significant difference in allele frequency (p = .044, OR = 1.54 95% CI = 1.02-2.33) between patients who developed tardive dyskinesia and those who did not. Significant difference remains even after adjusting for age and neuroleptic dosage (p = .041) with the odds ratio at 1.64 (95% CI 1.02-2.62).Conclusions: A genetic variant of the 5-HT2A receptor may be associated with neuroleptic-induced tardive dyskinesia in schizophrenia. Further studies are needed to replicate the finding. The role of 5-HT2A receptor in the etiology of tardive dyskinesia or treatment-resistant schizophrenia should be further investigated. (C) 2001 Society of Biological Psychiatry.