Association analysis of polymorphisms of the NTRK2 and BDNF genes with bipolar affective disorder in a Polish sample
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Arch Psych Psych 2010;12(2):5–16
Aims. Neurodevelopmental abnormality has been implicated in the pathogenesis of bipolar disorder. The neurotrophin BDNF regulates not only cell survival, proliferation and synaptic growth in the developing CNS, but also plays a crucial role in activity-dependent neuroplasticity. Substantial evidence has pointed to the role of the BDNF in the pathophysiology of mood disorders and in the mechanism of action of therapeutic agents. Consequently, BDNF and its receptor, encoded by the NTRK2 gene, constitute good candidates for molecular genetic studies in bipolar affective disorder (BPD). Methods. In the present study we selected four single nucleotide polymorphisms (SNPs) of the BDNF and three SNPs of the NTRK2 genes. The case-controlled analyses were performed on patients with bipolar disorders (n=455, control n=589) and in the subgroups of patients, formed by using the following criteria: the clinical type of BPD (BPD type I & II), gender, age of onset, family history of (BPD) and a history of suicidal attempts. Results. The haplotype GC (rs988748/rs203024) of the BDNF gene was significantly more frequent in patients with BPD then in controls (p=0.006). Also haplotype CA (rs 1187326/rs1187327) of the NTRK2 gene was significantly more frequent in patients than in the control group (p=0.046). Case-control analysis of single markers after adjusting the significance level for multiple tests did not show any significant differences. Conclusions. These data suggest that polymorphisms of BDNF and NTRK2 genes may be involved in the aetiology of bipolar disorder in the Polish population.