A search for a mutation associated with narcolepsy.

• Project/Area Number: 09670978
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Psychiatric science
• Research Institution: University of Tokyo
• Principal Investigator: FUKUDA Masato University of Tokyo, Department of Neuropsychiatry, Faculty of Medicine, Lecturer, 医学部・附属病院, 講師 (20221533)
• Co-Investigator(Kenkyū-buntansha): HONDA Yutaka Seiwa Hospital Neuropsychiatric Research Institute, Director, 附属晴和病院, 院長 ; 本多 真 東京都立松沢病院, 医員
• Project Period (FY): 1997 – 1998
• Project Status: Completed (Fiscal Year 1998)
• Budget Amount: ¥2,900,000 (Direct Cost: ¥2,900,000); Fiscal Year 1998: ¥800,000 (Direct Cost: ¥800,000); Fiscal Year 1997: ¥2,100,000 (Direct Cost: ¥2,100,000)
• Keywords: narcolepsy / tumor necrosis factor alpha / molecular genetics / ナルコレプシ-

Research Abstract

The striking evidence of almost 100% association of narcolepsy with HLA DR2(DR15) antigen is an important clue to elucidate molecular basis of this sleep disorder. The gene for tumor necrosis factor alpha (TNF alpha) is located in the HLA class II gene cluster. Recent studies have indicated that TNF alpha plays an important role in regulation of normal human sleep and regulation of this cytokine may be disturbed in narcolepsy. We searched for a mutation associated with narcolepsy in the TNF alpha gene by single-strand conformation polymorphism (SSCP) analysis. Twelve PCR fragments of 300-500bp covering promoter region, exons, and introns, are examined twice at two different experimental conditions. A novel polymorphism, C-850T, was found in the promoter region of the TNF alpha gene in narcoleptic patients. Genotype frequency was examined by restriction fragment length polymorphism method. No significant difference of genotype distribution was found between 92 patients with narcolepsy and 91 normal controls. These results do not support our hypothesis that genetic abnormality of TNF alpha production is pathogenetic for narcolepsy.

Research Products

• [Publications] Kato T,Fukuda M 他: "A novel polymorphism in the promoter region of the tumor necrosis factor alpha gene : No association with narcolepsy." American Journal of Medical Genetics. in press. (1999)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Kato T,Fukuda M 他: "A search for a mutation in the tumor necrosis factor alpha (TNF-α) gene in narcolepsy" Psychiatry and Clinical Neuroscience. in press. (1999)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Kato T,Fukuda M,et al.: "A novel polymorphism in the promoter region of the tumor necrosis factor alpha gene : No association with narcolepsy." American Journal of Medical Genetics. (in press).
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Kato T,Fukuda M,, et al.: "A search for a mutation in the tumor necrosis factor alpha(TNF-alpha)gene in narcolepsy." Psychiatry and Clinical Neuroscience. (in press).
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Kato T,Fukuda M 他: "A novel polymorphism in the promoter region of the tumor necrosis factor alpha gene : No association with narcolepsy." American Journal of Medical Genetics. (in press). (1999)
• [Publications] Kato T,Fukuda M 他: "A search for a mutation in the tumor necrosis factor alpha (TNF-α) gene in narcolensy" Psychiatry and Clinical Neuroscience. (in press). (1999)
• [Publications] Fukuda M., 他: "Behavioral and P3 amplitude enhancement in schizophrenia following feedback training" Shizophernia Research. 25・3. 231-242 (1997)