Relationships between polymorphisms of genes encoding neurotrophic factors and neurodevelopment in schizophrenia

神经营养因子基因的多态性可能参与了精神分裂症的发病机制。我们研究了神经营养素-3(NT-3)、脑源性神经营养因子(BDNF)和胶质细胞源性神经营养因子(GDNF)基因的多态性，并探讨了它们对精神分裂症易感性和神经发育异常的影响。在不考虑疾病严重程度的情况下，NT-3基因的Gly(-63)Glu多态性与精神分裂症的易感性没有显著关联。在NT-3基因的AP-1结合位点附近发现了核苷酸替换；然而，它与精神分裂症的易感性无关。先前报道的与精神分裂症风险相关的NT-3基因的二核苷酸重复多态与精神分裂症患者的海马体体积缩小有关，这表明该多态性可能通过包括海马区在内的中枢神经系统发育异常而对精神分裂症的发展产生影响。我们在BDNF基因的启动子和5个非翻译区发现了两个核苷酸替换。这些基因多态可能与精神分裂症的发病风险有关。根据《母婴健康手册》中的信息，我们证实了精神分裂症患者的产前发育不良，包括eNS.的发育，但Gly(-63)Glu或NT-3基因的二核苷酸重复序列多态性与精神分裂症患者出生时的头围没有明显的关联。

Polymorphisms of gens encoding neurotrophic factors are possibly involved in the pathogenesis of schizophrenia. We searched for polymorphisms in the neurotrophin-3 (NT-3), brain derived neurotrophic factor (BDNF), and glial cell-line derived neurotrophic factor (GDNF) genes and explored their effects on susceptibility and neurodevelopmental abnormalities in schizophrenia.The Gly(-63)Glu polymorphism of the NT-3 gene was not significantly associated with susceptibility to schizophrenia when severity of the disease was not taken into account. A nucleotide substitution was found in the vicinity of the AP-1 binding site of the NT-3 gene ; however, it was not associated with susceptibility to schizophrenia. A dinucleotide repeat polymorphism of the NT-3 gene, which was previously reported to be associated with the risk of schizophrenia, was found to be associated with reduced volume of hippocampi in schizophrenic subjects, suggesting that this polymorphism may exert an effect on the development of schizophrenia through neurodevelopmental abnormalities of the CNS including hippocampus. We found two nucleotide substitutions in the promoter and 5 untranslated regions of the BDNF gene. These polymorphisms were suggested to be associated with the risk of developing schizophrenia. We could not find any polymorphism for the GDNF gene.Based on information from the Maternal and Child Health Handbook, we confirmed the prenatal underdevelopment in schizophrenia, including development of the eNS.However, there was no significant association of Gly(-63)Glu or the dinucleotide repeat polymorphism of the NT-3 gene with head circumference at birth of schizophrenics.