Abstract
The association between BDNF gene functional Val66Met polymorphism rs6265 and the schizophrenia is far from being consistent. In addition to the heterogeneous in schizophrenia per se leading to the inconsistent results, the interaction among multi-genes is probably playing the main role in the pathogenesis of schizophrenia, but not a single gene. Neurotrophic tyrosine kinase receptor 2 (NTRK2) is the high-affinity receptor of BDNF, and was reported to be associated with mood disorders, though no literature reported the association with schizophrenia. Thus, in the present study, total 402 patients with paranoid schizophrenia (the most common subtype of schizophrenia) and matched 406 healthy controls were recruited to investigate the role of rs6265 in BDNF, three polymorphisms in NTRK2 gene (rs1387923, rs2769605 and rs1565445) and their interaction in the susceptibility to paranoid schizophrenia in a Chinese Han population. We did not observe significant differences in allele and genotype frequencies between patients and healthy controls for all four polymorphisms separately. The haplotype analysis also showed no association between haplotype of NTRK2 genes (rs1387923, rs2769605, and rs1565445) and paranoid schizophrenia. However, we found the association between the interaction of BDNF and NTRK2 with paranoid schizophrenia by using the MDR method followed by conventional statistical analysis. The best gene-gene interaction model was a three-locus model (BDNF rs6265, NTRK2 rs1387923 and NTRK2 rs2769605), in which one low-risk and three high-risk four-locus genotype combinations were identified. Our findings implied that single polymorphism of rs6265 rs1387923, rs2769605, and rs1565445 in BDNF and NTRK2 were not associated with the development of paranoid schizophrenia in a Han population, however, the interaction of BDNF and NTRK2 genes polymorphisms (BDNF-rs6265, NTRK2-rs1387923 and NTRK2-rs2769605) may be involved in the susceptibility to paranoid schizophrenia.
Highlights
Schizophrenia is a chronic, recurrent, disabling mental disease with a high cost to society and individuals across the world [1,2]
It is notable that Brain-derived neurotrophic factor (BDNF) most likely functions through its high-affinity receptor, neurotrophic tyrosine kinase receptor 2 (NTRK2) [11]; and NTRK2 has been found decreased in postmortem of schizophrenic subjects [12]
The aim of the present study is to investigate the role of BDNF functional Val66Met polymorphism, three polymorphisms in NTRK2 gene and their interaction in pathophysiology of paranoid schizophrenia
Summary
Schizophrenia is a chronic, recurrent, disabling mental disease with a high cost to society and individuals across the world [1,2]. Increasing postmortem studies have shown that BDNF levels were significantly lower in prefrontal cortex of schizophrenia patients [9,10]. It is notable that BDNF most likely functions through its high-affinity receptor, neurotrophic tyrosine kinase receptor 2 (NTRK2) [11]; and NTRK2 has been found decreased in postmortem of schizophrenic subjects [12]. Some previous study have demonstrated that BDNF and NTRK levels were both decreased in the brain tissue of schizophrenic patients [13,14]. All these evidence suggest that dysfunction of BDNF and TrkB may be involved in the pathophysiology underlying schizophrenia
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