Identification of two risk haplotypes for schizophrenia and bipolar disorder in the synaptic vesicle monoamine transporter gene (SVMT)

The synaptic vesicular monoamine transporter (SVMT) plays a key role in monoaminergic neuro-transmission determining the size of neurotransmitter vesicular pools available for exocytotic release. Recently, several lines of evidence have suggested that altered functions of SVMT may be involved in the pathogenesis of certain neuropsychiatric diseases, including psychotic and mood disorders. In the present study, we tested the potential involvement of SVMT gene variants in the etiology of schizophrenia and bipolar disorder. Five different SNPs (T440G, C1368T, T2666C, A2683C, and A745G) were included in the analysis covering a region of about 35 kb along the SVMT gene. Analyses were performed in a case-control sample consisting of 88 bipolar patients, 107 subjects with schizophrenia, and 164 controls. Two risk haplotypes for both schizophrenia and bipolar disorder in SVMT gene were identified. Particularly, 2666T-2683A-745G (TAG) and 2666C-2683C-745A (CCA) combinations were significantly more frequent in both bipolar and schizophrenic patients than in controls. UNPHASED package estimated haplotype effects for all patients yielded relative risks of 4.1 (95%CI: 1.83-9.21) for TAG combination and 2.336 (95%CI: 1.28-4.26) for CCA haplotype. Conversely, 2666T2683C-745A (TCA) and 2666C-2683A-745G (CAG) haplotypes seemed to protect against these mental disorders, since the estimated frequency in control chromosomes was 12% whilst such haplotypes were not observed in any bipolar or schizophrenic subject (P < 0.0000). Our results strongly suggest that SVMT gene or certain regions of it may constitute a genetic substrate of susceptibility for both schizophrenia and bipolar disorder. (c) 2007 Wiley-Liss, Inc.