BDNF gene is a genetic risk factor for schizophrenia and is related to the chlorpromazine-induced extrapyramidal syndrome in the Chinese population

Abstract

Brain-derived neurotrophic factor (BDNF) belongs to a family of the neurotrophin, which plays important roles in the neurodevelopment of dopaminergic-related systems and interacts with meso-limbic dopaminergic systems involved in the therapeutic response to antipsychotics. Functional experiments have suggested that BDNF may be involved in the etiology of schizophrenia. In this study, we genotyped two important functional polymorphisms in the BDNF gene using a sample of Han Chinese patients consisting of 340 schizophrenic patients and 343 healthy controls. We found a statistical difference in the 232-bp allele distribution of the BDNF gene (GT)n dinucleotide repeat polymorphism between the schizophrenic patients and controls. In early onset patients, the 234-bp allele had a risk role. For the chlorpromazine-induced extrapyramidal syndrome, the 230-bp allele and the 234-bp allele acted in opposite directions, that is, patients with the 230-bp allele of the (GT)n polymorphism exhibited a lower degree of induced extrapyramidal syndrome. Haplotype-based analysis also revealed a very important risk haplotype (P=0.0000226546). These findings suggest that BDNF plays an important role in the susceptibility to schizophrenia and that the (GT)n repeat polymorphism of the BDNF gene may be an independent contributor to the chlorpromazine treatment-sensitive form of schizophrenia.