Exon 3 of tyrosine hydroxylase gene

Lack of association with Japanese schizophrenic patients

M. Ota, Akira Nakashima, K. Ikemoto, S. Nojima, M. Tanaka, M. Okuda, H. Koga, K. Mori, Y. S. Kaneko, K. Fujiwara, H. Yamamoto, T. Nagatsu, A. Ota

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Tyrosine hydroxylase (TH) is the rate-limiting enzyme in dopamine (DA) biosynthesis. Exon 3 of the human TH gene encodes the sequence from Set31 to Glu104 of type 1 enzyme, 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. 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, 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. 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.

Original languageEnglish
Pages (from-to)315-319
Number of pages5
JournalMolecular Psychiatry
Volume6
Issue number3
DOIs
Publication statusPublished - 18-04-2001

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Tyrosine 3-Monooxygenase
Exons
Dopamine
Schizophrenia
Genes
Enzymes
Introns
Amino Acid Sequence
Alleles
Genotype
3-tyrosine
Amino Acids
Mutation
Brain

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

Cite this

Ota, M. ; Nakashima, Akira ; Ikemoto, K. ; Nojima, S. ; Tanaka, M. ; Okuda, M. ; Koga, H. ; Mori, K. ; Kaneko, Y. S. ; Fujiwara, K. ; Yamamoto, H. ; Nagatsu, T. ; Ota, A. / Exon 3 of tyrosine hydroxylase gene : Lack of association with Japanese schizophrenic patients. In: Molecular Psychiatry. 2001 ; Vol. 6, No. 3. pp. 315-319.
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abstract = "Tyrosine hydroxylase (TH) is the rate-limiting enzyme in dopamine (DA) biosynthesis. Exon 3 of the human TH gene encodes the sequence from Set31 to Glu104 of type 1 enzyme, 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. 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, 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. 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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Ota, M, Nakashima, A, Ikemoto, K, Nojima, S, Tanaka, M, Okuda, M, Koga, H, Mori, K, Kaneko, YS, Fujiwara, K, Yamamoto, H, Nagatsu, T & Ota, A 2001, 'Exon 3 of tyrosine hydroxylase gene: Lack of association with Japanese schizophrenic patients', Molecular Psychiatry, vol. 6, no. 3, pp. 315-319. https://doi.org/10.1038/sj.mp.4000840

Exon 3 of tyrosine hydroxylase gene : Lack of association with Japanese schizophrenic patients. / Ota, M.; Nakashima, Akira; Ikemoto, K.; Nojima, S.; Tanaka, M.; Okuda, M.; Koga, H.; Mori, K.; Kaneko, Y. S.; Fujiwara, K.; Yamamoto, H.; Nagatsu, T.; Ota, A.

In: Molecular Psychiatry, Vol. 6, No. 3, 18.04.2001, p. 315-319.

Research output: Contribution to journalArticle

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T2 - Lack of association with Japanese schizophrenic patients

AU - Ota, M.

AU - Nakashima, Akira

AU - Ikemoto, K.

AU - Nojima, S.

AU - Tanaka, M.

AU - Okuda, M.

AU - Koga, H.

AU - Mori, K.

AU - Kaneko, Y. S.

AU - Fujiwara, K.

AU - Yamamoto, H.

AU - Nagatsu, T.

AU - Ota, A.

PY - 2001/4/18

Y1 - 2001/4/18

N2 - Tyrosine hydroxylase (TH) is the rate-limiting enzyme in dopamine (DA) biosynthesis. Exon 3 of the human TH gene encodes the sequence from Set31 to Glu104 of type 1 enzyme, 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. 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, 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. 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.

AB - Tyrosine hydroxylase (TH) is the rate-limiting enzyme in dopamine (DA) biosynthesis. Exon 3 of the human TH gene encodes the sequence from Set31 to Glu104 of type 1 enzyme, 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. 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, 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. 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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