An Analysis of Five TrkB Gene Polymorphisms in Schizophrenia and the Interaction of Its Haplotype with rs6265 BDNF Gene Polymorphism.

Renata Suchanek-Raif,Jan Kowalski,Krzysztof Kucia,Wojciech Merk,Aleksandra Zielińska,Monika Paul-Samojedny,Paweł Raif,Małgorzata Kowalczyk

doi:10.1155/2020/4789806

Abstract

Aim The BDNF dysfunction in the schizophrenia has been soundly documented. The TrkB gene is a high-affinity receptor of the BDNF that is changed in schizophrenia and mood disorders. The study had two aims: first, to identify whether the five nucleotide polymorphisms (SNPs) in TrkB gene are associated with a diagnosis of schizophrenia; and the latter, if any association exists between the TrkB SNPs and psychopathology, suicide attempts, and family history of schizophrenia in a Caucasian population. Methods Case-control study (401 patients and 657 healthy controls) was used to examine a predisposition for schizophrenia. The tests for psychopathology, suicide attempts, and family history of schizophrenia were conducted only in patient group. The severity of the schizophrenia was measured using the five-factor model of the PANSS. In addition, the haplotype analysis for both the separate for SNPs of TrkB gene and in combination with the rs6265 SNP BDNF gene was conducted. Results Our case-control study revealed that the genetic variants of rs10868235 (T/T polymorphic genotype) and rs1387923 (G/G polymorphic genotype) of the TrkB gene were associated with a higher risk of developing schizophrenia in men. However, the A/A wild genotype of rs1387923 was connected with a lower risk for both the development of and the family manifestation of schizophrenia in men. The G polymorphic allele of rs1565445 was associated with an increased risk of suicide in schizophrenia. The tested SNPs of the TrkB gene did not modulate the psychopathology of schizophrenia. The haplotype that was built with five SNPs in the TrkB gene was protective for men, but after joining the rs6265 SNP of the BDNF gene, a haplotype that was protective for women was created.

Highlights

Schizophrenia is a severe, chronic mental disease with an etiology that is still not fully understood
We found that the A/A genotype of rs1387923 SNP was more frequent in male patients without relatives with schizophrenia than male patients with family history of schizophrenia
We found that the ATAAT haplotype was more frequent in control than in schizophrenia group (6% vs. 3%, respectively), and it was associated with a lower risk of schizophrenia, as well (OR = 0:44, 95% confidence interval (CI): 0.22-0.88, p < 0:05)

Summary

Introduction

Schizophrenia is a severe, chronic mental disease with an etiology that is still not fully understood. The TrkB (tropomyosin-related kinase B) receptor is involved in several important biological processes in neural tissues. This protein can promote both the prosurvival and the proapoptotic effects in response to neurotrophins. The TrkB receptor plays a critical role in signaling for the brain-derived neurotrophic factor (BDNF), which is one of the most important. The BDNF levels were lower in patients with schizophrenia in both the serum [1] and in the brain [3]. The levels of BDNF has been correlated with the intensity of the psychopathological symptoms in patients with schizophrenia [4, 5]. The evidence has revealed that the receptor TrkB levels are changed in schizophrenia patients. While the full-length TrkB levels were decreased, two truncated TrkB isoforms (trkB.t1 and trkB.shc) were increased in the prefrontal cortex [6, 7] and hippocampus in patients with schizophrenia [8]

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Results

Conclusion