Dubertret C, Hanoun N, Adès J, Hamon M, Gorwood P
Service de Psychiatrie Adultes, Faculty of Medicine Bichat-Claude Bernard, Hôpital Louis Mourier (AP-HP), 178 rue des Renouillers, 92701 Colombes Cedex, France.
Am J Med Genet B Neuropsychiatr Genet. 2004 Apr 1;126B(1):10-5. doi: 10.1002/ajmg.b.20120.
The expression of serotonin type 6 receptor (5-HT(6)) in limbic and cortical regions of the brain, and its high affinity for atypical antipsychotics suggest that its encoding gene may play a role in the pathogenesis of schizophrenia. We firstly performed a meta-analysis of the C267T polymorphism of the 5-HT(6) gene in schizophrenia, based on four different case/control studies, and showed that the allelic distribution is not significantly different between patients and controls, even when taking into account the role of between samples heterogeneity. We then recruited 103 trios (patients with Diagnostic and Statistical Manual Mental Disorders, 4th ed. (DSM-IV) diagnosis of schizophrenia and their parents), and investigated the C267T polymorphism of the 5-HT(6) receptor gene with regard to family-based association study approach (haplotype relative risk (HRR) and transmission disequilibrium test (TDT)). We found no excess of transmission of one allele from the parents to their affected children, using the HRR (P = 0.60), as well as no evidence for linkage between C267T polymorphism and schizophrenia, using the TDT (P = 0.71). Furthermore, the 267T allele frequency was comparable in the different subgroups defined on age at onset, family history of schizophrenia, treatment response, and subtypes of patients based on positive versus negative predominant symptoms. These data do not support the idea that the 5-HT(6) receptor gene plays a major role in the etiopathogenesis of schizophrenia.
血清素6型受体（5-HT(6)）在大脑边缘和皮质区域的表达，以及它对非典型抗精神病药物的高亲和力表明，其编码基因可能在精神分裂症的发病机制中起作用。我们首先基于四项不同的病例/对照研究，对精神分裂症患者5-HT(6)基因的C267T多态性进行了荟萃分析，结果显示，即使考虑样本间异质性的影响，患者和对照之间的等位基因分布也没有显著差异。然后，我们招募了103个三联体（诊断为精神分裂症的《精神疾病诊断与统计手册》第4版（DSM-IV）患者及其父母），并采用基于家系的关联研究方法（单倍型相对风险（HRR）和传递不平衡检验（TDT））研究了5-HT(6)受体基因的C267T多态性。我们发现，使用HRR方法时，父母向受影响子女传递一个等位基因的情况并未增多（P = 0.60），使用TDT方法时，也没有证据表明C267T多态性与精神分裂症之间存在连锁关系（P = 0.71）。此外，在根据发病年龄、精神分裂症家族史、治疗反应以及基于阳性或阴性为主症状定义的患者亚型所划分的不同亚组中，267T等位基因频率相当。这些数据不支持5-HT(6)受体基因在精神分裂症病因学中起主要作用这一观点。
