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

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.

BDNF gene Val66Met polymorphisms as a predictor for clinical presentation in schizophrenia – recent findings

“…Although sex as a distinguishing biological factor is crucial in genetic studies, the social construct of gender may further bring clarity, especially in the light of research highlighting more prevalent gender dysphoria in individuals with schizophrenia than in the general population ( 53 ). Sex differences were found in the risk of developing schizophrenia by Shuchanek-Raif ( 35 ). In this study, the ATAAT haplotype (built with 5 SNPs in the TrKB gene) was associated with a lower risk for schizophrenia in men.…”

“…Multiple genetic interactions were explored by Su ( 41 ), Morozova ( 40 ), Zzhang ( 28 ), Kim and Kim ( 25 ), Sosin ( 30 ), Pan ( 43 ), Karacetin ( 38 ), Ping ( 45 ), and Suchanek-Raif ( 35 ), revealing various associations or propensity for risk for schizophrenia.…”

Morphogenetic theory of mental and cognitive disorders: the role of neurotrophic and guidance molecules

“…Overall, these defects may ultimately lead to neurological and psychiatric disorders. For example, in a Polish population the polymorphisms of the BDNF receptor-TrkB (NTRK2 gene): rs10868235-T (intr) and rs1387923-G (3′UTR) was found to be associated with a higher risk of schizophrenia in men; rs1387923-A (3′UTR)-with a lower risk of schizophrenia, and the polymorphism rs1565445-A (intr)-with an increased risk of suicide in schizophrenia (Suchanek-Raif et al, 2020). It is worth noting that many of the described TrkB SNPs are associated with the predisposition to suicidal activity; therefore, it is suggested that NTRK2 polymorphisms should be screened for if there was a history of suicidal ideation.…”

Associations of BDNF/BDNF-AS SNPs with Depression, Schizophrenia, and Bipolar Disorder

“…However, when the rs6265 SNP of the BDNF gene was added, a specific GTAGCG haplotype was observed, which demonstrated protective effects exclusively in women. These findings were particularly significant for the paranoid subtype of schizophrenia without concomitant depressive episodes [ 106 ].…”