Bipolar disorder and DNA methylation of serotonin transporter

  • Ogata Yu
    Department of Molecular Psychiatry, Graduate School of Medicine, the University of Tokyo Department of Neuropsychiatry, Graduate School of Medicine, the University of Tokyo
  • Ikegame Tempei
    Department of Molecular Psychiatry, Graduate School of Medicine, the University of Tokyo Department of Neuropsychiatry, Graduate School of Medicine, the University of Tokyo
  • Bundo Miki
    Department of Molecular Psychiatry, Graduate School of Medicine, the University of Tokyo
  • Kasai Kiyoto
    Department of Neuropsychiatry, Graduate School of Medicine, the University of Tokyo
  • Iwamoto Kazuya
    Department of Molecular Psychiatry, Graduate School of Medicine, the University of Tokyo

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Other Title
  • セロトニントランスポーターの DNA メチル化と精神疾患
  • セロトニントランスポーター ノ DNA メチルカ ト セイシン シッカン

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Abstract

SLC6A4 (solute carrier family 6, member 4) gene encodes a serotonin transporter (5-hydroxytryptamine transporter, HTT) , whose epigenetic regulation is assumed to be related to occurrence of mental disorders such as major depression and bipolar disorder. DNA methylation at the promoter CpG island and CpG island shore region inversely correlates with gene expression level. A functional polymorphism, HTT- linked polymorphic region (HTTLPR) and DNA methylation are thought to regulate gene expression of SLC6A4 cooperatively. By examining brain and peripheral blood samples, hypermethylation of SLC6A4 at the CpG island shore in bipolar disorder was identified. DNA methylation at the same CpG site was down- regulated in human neuroblastoma cells treated with mood stabilizers. DNA methylation of SLC6A4 at the CpG island shore can become sensitive marker of gene- environment interaction in mental disorders.

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