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

神经营养因子基因多态性可能参与精神分裂症的发病。我们寻找神经营养素-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，并探讨它们对精神分裂症易感性和神经发育异常的影响。当不考虑疾病的严重程度时，NT-3基因的Gly（-63）Glu多态性与精神分裂症易感性无显著相关性。在NT-3基因的AP-1结合位点附近发现了一个核苷酸取代，然而，它与精神分裂症的易感性无关。一个二核苷酸重复多态性的NT-3基因，这是以前报道与精神分裂症的风险，被发现与减少体积的海马在精神分裂症的主题，这表明，这种多态性可能会产生影响精神分裂症的发展，通过神经发育异常的中枢神经系统，包括海马。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。这些多态性被认为与精神分裂症的发病风险有关。我们没有发现GDNF基因的任何多态性。根据妇幼保健手册中的信息，我们证实了精神分裂症的产前发育不足，包括eNS的发展。然而，Gly（-63）Glu或NT-3基因的二核苷酸重复多态性与精神分裂症患者出生时的头围没有显著关联。

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.