Analysis of synapsin III-196 promoter mutation in schizophrenia and bipolar disorder

Neuropsychobiology
Herbert M LachmanTakuya Saito

Abstract

The 22q13-linked gene synapsin III is a positional candidate gene for schizophrenia (SZ). One interesting synapsin III single nucleotide polymorphism (SNP), -196G/A, has been identified in the promoter region. The -196A allele results in a 6/8 base match to the core recognition octamer sequence for Oct-1, a member of the POU family of transcription factors. To determine whether or not the -196 SNP is associated with either SZ or bipolar disorder (BD). A case control comparison was used to determine whether or not differences in allele or genotype distribution occurred in patients with SZ and BD. Electromobility gel shift assay (EMSA) was used to determine whether the -196 SNP affected protein binding. A trend towards significance was detected when the allele distribution was analyzed in Caucasian patients with SZ (n = 145; 191 controls) and a cohort of subjects from the Czech Republic with BD (n = 82; 94 controls). No association was found in bipolar patients from the United States (n = 127) or in African-American patients with SZ (n = 124; 133 controls). EMSA showed that the region encompassing the -196 SNP binds to a brain protein in an allele-specific manner. These data, while inconclusive, suggest that -196 SNP should be fu...Continue Reading

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