JP2006000015A - ストレスの評価方法 - Google Patents
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- JP2006000015A JP2006000015A JP2004177147A JP2004177147A JP2006000015A JP 2006000015 A JP2006000015 A JP 2006000015A JP 2004177147 A JP2004177147 A JP 2004177147A JP 2004177147 A JP2004177147 A JP 2004177147A JP 2006000015 A JP2006000015 A JP 2006000015A
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Abstract
【解決手段】 被験者の末梢血由来のメッセンジャーRNAにおいて、ストレスの評価マーカーとなる特定遺伝子群の発現プロファイルを解析し、その解析結果に基づいて該被験者のストレスを評価する。
【選択図】 図6
Description
また別な態様において、本発明の方法は、被験者の末梢血由来のメッセンジャーRNAにおいて、表1及び表2に示される遺伝子群から選ばれる遺伝子の発現量を解析し、その解析結果に基づいて該被験者のストレスを評価する方法であって、前記遺伝子が少なくとも表3に示される10遺伝子及び/又は表4に示される11遺伝子を含むことを特徴とする、ストレスの評価方法である。
発明者らは、精神疾患に罹患していないことが確認された健常人から得た全血よりRNAを抽出し、DNAチップを用いて1500の遺伝子の発現量を網羅的に解析し、その結果に基づいてストレスの評価マーカーとなる遺伝子群を決定した。DNAチップとは、ガラス等の支持基体上に多数の遺伝子に相当する塩基配列を有するDNA断片を固定化したものであり、ハイブリダイゼーションにより、サンプル中のRNAを検出するものである。解析は遺伝子の網羅的な発現解析が可能であれば、上記DNAチップに代えて、他のDNA固相化試料(DNAアレイ、キャピラリー、メンブレンフィルター等)や定量法を利用してもよい。なお、本発明において、「ストレス」とは運動や痛み等の物理的ストレスではなく、緊張、不安、恐怖等の精神的なストレスを意味する。
ストレスの評価マーカーとして選定された遺伝子群には、アポトーシス関連遺伝子、ATPase関連遺伝子、細胞周期関連遺伝子、サイトカイン関連遺伝子、熱ショックタンパク質関連遺伝子、ポリメラーゼ関連遺伝子、GTP結合タンパク質関連遺伝子、プロテインキナーゼC関連遺伝子、ミトコンドリアのストレス応答性チトクロームCオキシダーゼ関連遺伝子、ガン関連遺伝子が多く含まれている。
本発明は、上記実験結果に基づき完成されたものであり、被験者の末梢血からメッセンジャーRNAを用いて、ストレスの評価マーカーとなる特定遺伝子群の発現プロファイルを解析し、その解析結果に基づいて該被験者のストレスを評価する方法に関する。本発明のストレスの評価方法の概念図を図6に示す。
修論発表を控えた学生を対象として、修論発表の4週間前のサンプルを平常時の基準としたときの修論発表の直前と、直後、発表後の翌日における、メッセンジャーRNA発現量を比較した。
徳島大学医学部で修論発表を控えた学生のうち、本診断法開発のための研究に参加することについて文書により説明し同意を得たものを対象とした。本研究は徳島大学医学部附属病院倫理委員会の承認を得ている。対象となった10名の健常人は、男性2名、女性8名、年齢は24歳から27歳まで(平均24.9歳)だった。
30組すべてのデータで蛍光強度が300以上である遺伝子群(519個)を選び、この遺伝子群をグループ分けするクラスタ解析を行った。図1に519遺伝子の発現解析結果を示す。図1−1〜11は、各遺伝子の発現強度比(Cy5/Cy3)であり、図1−12は、クラスタ解析結果を示すカラーチャートである。図中、サンプル番号(1-10)は被験者番号に該当し、実験番号Aは、修士論文発表直前(Cy5)と修士論文発表4週間前(平常時)(Cy3)との比較、実験番号Bは、同一人物の修士論文発表直後(Cy5)と平常時(Cy3)との比較、実験番号Cは同一人物の修士論文発表後翌日(cy5)と平常時(cy3)との比較である。
前記実施例の比較対照として、音楽鑑賞等のストレスには無関係の刺激によって、ストレスの評価マーカー遺伝子群の発現量がどのように変動するかを確認した。
1.試験方法
20〜40代の健常人13人(サンプルNo.11−23)に、音楽鑑賞をしてもらい、その直後に静脈から5ccの血液を採血し、実施例1と同様に、トータルRNAを抽出した。抽出されたトータルRNA量は6〜20μgであった。
表1及び表2に記載した遺伝子群の鑑賞前と鑑賞後の発現強度比を図4−1及び図5−1に示す。ストレスの評価マーカーとして有用であると判断したこれら遺伝子群の発現量には、大きな変動が殆どみられなかった。したがって、表1及び表2に記載された遺伝子群の発現変動は、精神的なストレス刺激を受けた場合にのみ特徴的に起こることが確認された。
Claims (10)
- 被験者の末梢血由来のメッセンジャーRNAにおいて、表3に示される10遺伝子を含む遺伝子の発現量を解析し、その解析結果に基づいて該被験者のストレスを評価することを特徴とする、ストレスの評価方法。
- 被験者の末梢血由来のメッセンジャーRNAにおいて、表3に示される10遺伝子及び/又は表4に示される11遺伝子を含む遺伝子の発現量を解析し、その解析結果に基づいて該被験者のストレスを評価することを特徴とする、ストレスの評価方法。
- 被験者の末梢血由来のメッセンジャーRNAにおいて、表1及び表2に示される遺伝子群から選ばれる遺伝子の発現量を解析し、その解析結果に基づいて該被験者のストレスを評価する方法であって、前記遺伝子が少なくとも表3に示される10遺伝子を含むことを特徴とする、ストレスの評価方法。
- 被験者の末梢血由来のメッセンジャーRNAにおいて、表1及び表2に示される遺伝子群から選ばれる遺伝子の発現量を解析し、その解析結果に基づいて該被験者のストレスを評価する方法であって、前記遺伝子が少なくとも表3に示される10遺伝子及び/又は表4に示される11遺伝子を含むことを特徴とする、ストレスの評価方法。
- ユニバーサルRNAサンプルの遺伝子発現プロファイルと被験者の遺伝子発現プロファイルとを比較解析することにより、該被験者のストレスを評価することを特徴とする、請求項1〜4のいずれか1項に記載のストレスの評価方法。
- 同一被験者の平常時における遺伝子発現プロファイルとストレス負荷時における遺伝子発現プロファイルとを比較解析することにより、該被験者のストレスを評価することを特徴とする、請求項1〜4のいずれか1項に記載のストレスの評価方法。
- 前記遺伝子の発現量が、チップ、アレイ、メンブレンフィルター、及びキャピラリーを含むDNA固相化試料を用いて解析されることを特徴とする、請求項1〜6のいずれか1項に記載のストレスの評価方法。
- 表1及び表2に示される遺伝子から選ばれるいずれか1の遺伝子に特異的にハイブリダイズし、該遺伝子を検出するためのプローブを固相上に固定した、ストレス評価用固相化試料であって、
前記遺伝子として、少なくとも表3に示される10遺伝子を含むことを特徴とする、前記ストレス評価用固相化試料。 - さらに、表4に示される11遺伝子を検出するためのプローブが固相上に固定されていることを特徴とする、請求項8記載のストレス評価用固相化試料。
- 請求項1〜7のいずれか1項に記載のストレスの評価方法を実施するためのシステムであって、被験者の遺伝子発現データと、あらかじめ取得しておいた被験者の平常時の遺伝子発現データ又はユニバーサルRNAサンプルの遺伝子発現データとを比較解析する手段を備えていることを特徴とする、ストレス評価システム。
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WO2008016101A1 (fr) | 2006-08-04 | 2008-02-07 | Ajinomoto Co., Inc. | Procédé d'évaluation de stress, appareil d'évaluation de stress, système d'évaluation de stress, programme d'évaluation de stress et support d'enregistrement associé |
JP2011167149A (ja) * | 2010-02-22 | 2011-09-01 | National Institute Of Advanced Industrial Science & Technology | 実験動物飼育管理手法およびキット |
JP2013150558A (ja) * | 2012-01-24 | 2013-08-08 | Kyushu Univ | 疲労状態及びストレス状態の評価方法 |
KR102135178B1 (ko) * | 2019-01-15 | 2020-07-17 | 한남대학교 산학협력단 | 고중력에 노출된 쥐의 유전자 분석방법 |
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US8492096B2 (en) * | 2008-12-24 | 2013-07-23 | Boris Pasche | TGFBR1 expression modifies risk for colorectal cancer |
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WO2008016101A1 (fr) | 2006-08-04 | 2008-02-07 | Ajinomoto Co., Inc. | Procédé d'évaluation de stress, appareil d'évaluation de stress, système d'évaluation de stress, programme d'évaluation de stress et support d'enregistrement associé |
US8673647B2 (en) | 2006-08-04 | 2014-03-18 | Ajinomoto Co., Inc. | Stress evaluating apparatus, method, system and program and recording medium therefor |
JP2011167149A (ja) * | 2010-02-22 | 2011-09-01 | National Institute Of Advanced Industrial Science & Technology | 実験動物飼育管理手法およびキット |
JP2013150558A (ja) * | 2012-01-24 | 2013-08-08 | Kyushu Univ | 疲労状態及びストレス状態の評価方法 |
KR102135178B1 (ko) * | 2019-01-15 | 2020-07-17 | 한남대학교 산학협력단 | 고중력에 노출된 쥐의 유전자 분석방법 |
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