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Analysis of Enhancer Activity of a Dinucleotide Repeat Polymorphism in the Neurotrophin-3 Gene and Its Association with Bipolar Disorder

Tadokoro K.a · Hashimoto R.a · Tatsumi M.b · Kamijima K.b · Kunugi H.a
aDepartment of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Ogawahigashi, Kodaira, and bDepartment of Psychiatry, Showa University School of Medicine, Tokyo, Japan Neuropsychobiology 2004;50:206–210 (DOI:10.1159/000079971)

Abstract

Growing evidence has implicated the possible involvement of neurotrophins in the pathogenesis of functional psychoses such as schizophrenia and bipolar disorder. Previous studies reported a significant association of a dinucleotide repeat polymorphism of the neurotrophin-3 (NTF3) gene with schizophrenia. The aims of the present study were to examine whether this polymorphism is associated with bipolar disorder and whether the polymorphic region has an enhancer/silencer effect on transcriptional activity in an allele-dependent manner. In an association analysis between the polymorphism and bipolar disorder in a Japanese sample of 88 patients and 98 controls matched for age, sex, and ethnicity, the distribution of alleles did not differ significantly between the two groups. pGL3-promoter luciferase reporter vectors containing the polymorphic region increased luciferase activity relative to empty pGL3-promoter vector in HeLa, IMR-32 (neuroblastoma) and Hs683 (glioma) cell lines; however, no significant difference was detected between alleles for either cell line. Our results suggest that the examined polymorphism has no major role in giving susceptibility to bipolar disorder. Although the polymorphic region may have an enhancer-like effect on transcriptional activity, we obtained no evidence for allele-dependent differential effects.

 

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