Department of Psychiatry, Kaohsiung Armed Forces General Hospital, Kaohsiung, Taiwan.
BMC Med Genet. 2009 Dec 29;10:147. doi: 10.1186/1471-2350-10-147.
The tumour supressor gene TP53 is thought to be involved in neural apoptosis. The polymorphism at codon 72 in TP53 and the long form variants of the upstream variable number of tandem repeats (uVNTR) polymorphism in the dopamine D4 receptor (DRD4) gene are reported to confer susceptibility to schizophrenia.
We recruited 934 patients with schizophrenia and 433 healthy individuals, and genotyped the locus of the TP53 codon 72 and DRD4 uVNTR polymorphisms by combining the polymerase chain reaction-restriction fragment length polymorphism method (PCR-RFLP) with direct sequencing.
No significant differences were found in the frequency of the genotype of the TP53 codon72 polymorphism between patients with schizophrenia and their controls. However, the long form alleles (> or = 5 repeats) of the DRD4 uVNTR polymorphism were more frequent in patients with schizophrenia than in controls (p = 0.001). Hence, this class of alleles might be a risk factor for enhanced vulnerability to schizophrenia (odds ratio = 3.189, 95% confidence interval = 1.535-6.622). In the logistic regression analysis, the long form variants of the DRD4 polymorphism did predict schizophrenia after the contributions of the age and gender of the subjects were included (p = 0.036, OR = 2.319), but the CC and GG genotypes of the codon 72 polymorphism of TP53 did not.
The long form variants of the uVNTR polymorphism in DRD4 were associated with schizophrenia, in a manner that was independent of the TP53 codon 72 polymorphism. In addition, given that the genetic effect of the TP53 codon 72 polymorphism on the risk of developing schizophrenia was very small, this polymorphism is unlikely to be associated with schizophrenia. The roles that other single nucleotide polymorphisms (SNPs) in the TP53 gene or in other apoptosis-related genes play in the synaptic dysfunction involved in the pathogenesis of schizophrenia should be investigated.
肿瘤抑制基因 TP53 被认为参与神经细胞凋亡。TP53 密码子 72 多态性和多巴胺 D4 受体（DRD4）基因上游可变数串联重复（VNTR）多态性的长等位基因被报道与精神分裂症易感性相关。
我们招募了 934 名精神分裂症患者和 433 名健康对照者，采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）联合直接测序法检测 TP53 密码子 72 多态性和 DRD4 uVNTR 多态性的基因型。
精神分裂症患者与对照组之间 TP53 密码子 72 多态性的基因型频率无显著差异。然而，DRD4 uVNTR 多态性的长等位基因（≥5 个重复）在精神分裂症患者中比对照组更为常见（p = 0.001）。因此，这类等位基因可能是增加精神分裂症易感性的危险因素（比值比=3.189，95%置信区间=1.535-6.622）。在逻辑回归分析中，在纳入研究对象的年龄和性别因素后，DRD4 多态性的长等位基因变体可以预测精神分裂症（p = 0.036，OR = 2.319），但 TP53 密码子 72 多态性的 CC 和 GG 基因型则不然。
DRD4 uVNTR 多态性的长等位基因变体与精神分裂症相关，且与 TP53 密码子 72 多态性无关。此外，鉴于 TP53 密码子 72 多态性对精神分裂症发病风险的遗传效应非常小，该多态性与精神分裂症无关。TP53 基因或其他与凋亡相关基因中的其他单核苷酸多态性（SNP）在精神分裂症发病机制中的突触功能障碍中所起的作用应进一步研究。
