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  • Original Research Article
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Exon 3 of tyrosine hydroxylase gene: lack of association with Japanese schizophrenic patients

Molecular Psychiatry volume 6, pages 315–319 (2001)Cite this article

Abstract

Tyrosine hydroxylase (TH) is the rate-limiting enzyme in dopamine (DA) biosynthesis.1,2 Exon 3 of the human TH gene encodes the sequence from Ser31 to Glu104 of type 1 enzyme,3,4 which contains the critical parts for regulation of the catalytic activity. The amino acid residues Gly36-Arg37-Arg38 were identified as a key sequence for DA to exert its inhibitory effect on catalytic activity.5–7 Therefore, we screened the nucleotide sequences of exon 3 from 201 Japanese patients with schizophrenia to explain the elevation in the synaptic or presynaptic DA concentrations in the schizophrenic brain,8–11 based on the hypothesis that any mutation changing the amino acid sequence Gly36-Arg37-Arg38 would result in the elevation of DA synthesis, due to a reduced inhibitory effect of DA on the catalytic activity.5–7 However, no mutated sequences of exon 3 and both exon–intron boundaries were detected in any of the patients examined. Polymorphisms generating Val81 and Met81 were compared of the distributions of genotype and allele between the patients and 175 Japanese healthy controls, which did not suggest an association between the polymorphism and schizophrenia. These results indicate that exon 3 of the human TH gene lacks association with schizophrenia in Japanese patients.

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Acknowledgements

We would like to express our gratitude to all patients and control individuals for their participation in this study. We also thank to Dr Y Ono (Fujita Health University) for his critical reading of the manuscript. This study was supported by grants-in-aid from Fujita Health University, Japan, to A Ota.

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Authors and Affiliations

  1. Department of Neuropsychiatry, Tosei General Hospital, Seto, 489–8642, Japan

    M Ota

  2. Department of Psychiatry, Nagoya City University Medical School, Nagoya, 467–8601, Japan

    M Ota

  3. Department of Physiology, Fujita Health University School of Medicine, Toyoake, 470–1192, Japan

    A Nakashima, K Mori, Y S Kaneko & A Ota

  4. Department of Anatomy, Fujita Health University School of Medicine, Toyoake, 470–1192, Japan

    K Ikemoto

  5. Kitatsushima Hospital, Heiwa-cho, 490–1300, Japan

    S Nojima

  6. Minamichita Hospital, Minamichita-cho, 470–3411, Japan

    M Tanaka

  7. Yagoto Hospital, Nagoya, 468–0073, Japan

    M Okuda

  8. Department of Neurology, Fujita Health University School of Medicine, Toyoake, 470–1192, Japan

    H Koga & H Yamamoto

  9. Department of Internal Medicine, Fujita Health University School of Medicine, Toyoake, 470–1192, Japan

    K Fujiwara

  10. Institute for Comprehensive Medical Sciences, Fujita Health University, Toyoake, 470–1192, Japan

    T Nagatsu

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  1. M Ota
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  2. A Nakashima
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  11. H Yamamoto
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Correspondence to A Ota.

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Ota, M., Nakashima, A., Ikemoto, K. et al. Exon 3 of tyrosine hydroxylase gene: lack of association with Japanese schizophrenic patients. Mol Psychiatry 6, 315–319 (2001). https://doi.org/10.1038/sj.mp.4000840

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  • DOI: https://doi.org/10.1038/sj.mp.4000840

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