気分障害の薬物反応性関連遺伝子ならびに疾患脆弱性遺伝子の検討

• Project/Area Number: 15790639
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Psychiatric science
• Research Institution: Fujita Health University
• Principal Investigator: 北島 剛司 藤田保健衛生大学, 医学部, 講師 (40360234)
• Project Period (FY): 2003 – 2005
• Project Status: Completed (Fiscal Year 2005)
• Budget Amount: ¥3,400,000 (Direct Cost: ¥3,400,000); Fiscal Year 2005: ¥1,100,000 (Direct Cost: ¥1,100,000); Fiscal Year 2004: ¥1,100,000 (Direct Cost: ¥1,100,000); Fiscal Year 2003: ¥1,200,000 (Direct Cost: ¥1,200,000)
• Keywords: 気分障害 / セロトニン / 関連研究 / 薬物反応性 / 大うつ病性障害 / セロトニン受容体 / 選択的セロトニン再取り込み阻害薬 / 双極性障害 / 変異検索

Research Abstract

当院を受診したDSMIVで診断された105人の大うつ病性障害の患者に対して選択的セロトニン再取り込み阻害薬(SSRI)であるFluvoxamineを投与し、投与前と投与8週後ハミルトン抑うつ評価尺度(HAM-D)の得点を評価すると共に、倫理審査委員会の承認に基づいて説明と同意の上、遺伝子検体を得た。このうち、投与前のHAM-Dが15点以上である84サンプルを解析対象とした。気分障害の疾患脆弱性や薬物反応性との関係が推測されるCRHR1、OPRS1、セロトニン1A、1B、1E受容体遺伝子を候補遺伝子として選定した。それぞれの遺伝子についてHapMapなどの既存のデータベースから日本人におけるLDブロックを推測し、これに基づいて頻度の高い一塩基多型(SNP)をhtSNPとして選択し、RFLP法、ダイレクトシークエンス法(サイクルシークエンス法による)によってgenotypingを施行した。HAM-Dの得点変化から反応・非反応群に分け、アレルワイズとハプロタイプワイズ双方で関連解析を行った(解析にはソフトウェアとしてSAS genetics, PowerMarkerを使用した)。CRHR1、OPRS1、セロトニン1A、1B、1E受容体のいずれの遺伝子についてもFLVの反応性との間に有意な関連は認められなかった。
なお、研究補助金は上記のサイクルシークエンス法、RFLP法、これらの基礎となるPCR法を行うための試薬などの消耗品の購入に活用された。

Research Products

• [Journal Article] No association of complexin1 and complexin2 genes with schizophrenia in a Japanese population (2006)
  • Author(s): Kishi, T.Ikeda, M.Suzuki, T.Kitajima, T.et al.
  • Journal Title: Schizophr Res 82(2-3) Pages: 185-189
• [Journal Article] Positive Association of the Serotonin 5-HT(7) Receptor Gene with Schizophrenia in a Japanese Population. (2006)
  • Author(s): Ikeda M, Iwata N, Kitajima T, Suzuki T
  • Journal Title: Neuropsychopharmacology 31(4) Pages: 866-871
• [Journal Article] No association was found between a functional SNP in ZDHHC8 and schizophrenia in a Japanese case-control population. (2005)
  • Author(s): Saito S, Ikeda M, Iwata N, Suzuki T, Kitajima T et al.
  • Journal Title: Neurosci Lett 374(1) Pages: 21-24
• [Journal Article] No association with the calcineurin A gamma subunit gene (PPP3CC) haplotype to Japanese schizophrenia. (2005)
  • Author(s): Kinoshita Y, Suzuki T, Ikeda M, Kitajima T et al.
  • Journal Title: J Neural Transm 112(9) Pages: 1255-1262
• [Journal Article] Association Analysis of Chromosome 5 GABA(A) Receptor Cluster in Japanese Schizophrenia Patients. (2005)
  • Author(s): Ikeda M, Iwata N, Suzuki T, Kitajima T et al.
  • Journal Title: Biol Psychiatry 58(6) Pages: 440-445
• [Journal Article] No association of GSK3beta gene (GSK3B) with Japanese scizophrenia. (2005)
  • Author(s): Ikeda M, Iwata N, Suzuki T, Kitajima T et al.
  • Journal Title: Am J Med Genet B Neuropsychiatr Genet 134(1) Pages: 90-92
• [Journal Article] Haplotype association between GABAA receptor g2 subunit gene (GABRG2) and methamphetamine use disorder (2005)
  • Author(s): Nishiyama T, Ikeda M, Iwata N, Kitajima T et al.
  • Journal Title: The Pharmacogenetics journal 5 Pages: 89-95
• [Journal Article] Association study of the calcineurin A-gamma subunit gene (PPP3CC) haplotype in Japanese schizophrenia (2005)
  • Author(s): Kinoshita Y, Ikeda M, Iwata T, Kitajima T et al.
  • Journal Title: Journal of Neural Transmission (in press)
• [Journal Article] Association of AKT1 with schizophrenia confirmed in A Japanese population (2004)
  • Author(s): Ikeda M, Iwata N, Suzuki T, Kitajima T et al.
  • Journal Title: Biological Psychiatry 56 Pages: 698-700
• [Journal Article] Personality of seasonal affective disorder analyzed by Tri-dimensional Personality Questionnaire (2004)
  • Author(s): Maeno N, Kusunoki K, Kitajima T, Iwata N et al.
  • Journal Title: Journal of Affective Disorders 85 Pages: 267-273
• [Publications] Kitajima T, Kanbayashi T, Saito Y, Ogawa Y, et al.: "Diazepan reduces both arterial blood pressure and muscle sympathetic nerve activity in human"Neuroscience letters. 355(1-2). 77-80 (2004)
• [Publications] Suzuki T, Iwata N, Kitajima T, Ozaki N, et al.: "Association of Novel Genetic Variants in the Serotonin 5-HT4 Receptor Gene (HTR4) with Japanese Schizophrenia."Am J Med Genet.. 121B(1). 7-13 (2003)
• [Publications] Yamanoushi Y, Iwata N, Suzuki T, Kitajima T, 他: "Effect of DRD2,5-HT2A, and COMT Genes on Antipsychotic Response to Risperidone."The Pharmacogenomics Journal. 3. 356-361 (2003)
• [Publications] Arinami T, Kitajima T, Yamanouchi Y, Iwata N, et al.: "Initial genome-wide scan for linkage with schizophrenia in the Japanese Schizophrenia Sib-pair Linkage Group (JSSLG) families."Am J Med Genet.. 120B. 22-28 (2003)
• [Publications] Kusunoki K, Kitajima T, Ozaki N.: "Does quazepam influence sleep and daytime activity in health adults?"Sleep and Biological Rhythms. 1(2). 171-172 (2003)
• [Publications] Ogawa Y, Kanbayashi T, Saito Y, Kitajima T et al.: "Total Sleep Deprivation Elevates Blood Pressure through Arterial Baroreflex Resetting - A Study with Microneurographic Technique."Sleep. 26(8). 986-989 (2003)