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J-GLOBAL ID：201802217935583832   整理番号：18A0844641

小児喘息におけるDNAメチル化:エピゲノム全体のメタ分析【JST・京大機械翻訳】

DNA methylation in childhood asthma: an epigenome-wide meta-analysis

著者 (108件)： Xu Cheng-Jian (Department of Pulmonology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands) ,  Xu Cheng-Jian (GRIAC research institute Groningen, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands) ,  Xu Cheng-Jian (Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands) ,  Soderhaell Cilla (Department of Women’s and Children’s Health, Karolinska Institutet, Stockholm, Sweden) ,  Soderhaell Cilla (Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden) ,  Bustamante Mariona (ISGlobal, Centre for Research in Environmental Epidemiology, the Barcelona Institute of Science and Technology, Barcelona, Spain) ,  Bustamante Mariona (Centre for Genomic Regulation, the Barcelona Institute of Science and Technology, Barcelona, Spain) ,  Bustamante Mariona (Universitat Pompeu Fabra, Barcelona, Spain) ,  Bustamante Mariona (CIBER Epidemiologia y Salud Publica (CIBERESP), Madrid, Spain) ,  Baiez Nour (Epidemiology of Allergic and Respiratory Diseases Department (EPAR), Sorbonne Universite, INSERM, Pierre Louis Institute of Epidemiology and Public Health, Saint-Antoine Medical School, Paris, France) ,  Gruzieva Olena (Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden) ,  Gehring Ulrike (Institute for Risk Assessment Sciences, Utrecht University, the Netherlands) ,  Mason Dan (Bradford Institute for Health Research, Bradford Teaching Hospitals NHS Foundation Trust, Bradford, UK) ,  Chatzi Leda (Department of Preventive Medicine, Keck School of Medicine, University of Southern California, LA, USA) ,  Chatzi Leda (Department of Social Medicine, Faculty of Medicine, University of Crete, Heraklion, Crete, Greece) ,  Chatzi Leda (Department of Genetics and Cell Biology, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, the Netherlands) ,  Basterrechea Mikel (CIBER Epidemiologia y Salud Publica (CIBERESP), Madrid, Spain) ,  Basterrechea Mikel (Health Research Institute Biodonostia, San Sebastian, Spain) ,  Basterrechea Mikel (Public Health Department of Gipuzkoa, San Sebastian, Spain) ,  Llop Sabrina (CIBER Epidemiologia y Salud Publica (CIBERESP), Madrid, Spain) ,  Llop Sabrina (Epidemiology and Environmental Health Joint Research Unit, FISABIO-Universitat Jaume I-Universitat de Valencia, Valencia, Spain) ,  Torrent Maties (ib-salut, Area de Salut de Menorca, Menorca, Spain) ,  Forastiere Francesco (Department of Epidemiology Lazio Regional Health Service, Rome, Italy) ,  Fantini Maria Pia (Department of Biomedical and Neuromotor sciences, University of Bologna, Bologna, Italy) ,  Carlsen Karin C Lodrup (Department of Paediatrics, Oslo University Hospital, Oslo, Norway) ,  Carlsen Karin C Lodrup (Department of Paediatric and Adolescent Medicine, University of Oslo, Oslo, Norway) ,  Haahtela Tari (Skin and Allergy Hospital, Helsinki University Hospital, University of Helsinki, Helsinki, Finland) ,  Morin Andreanne (Department of Human Genetics, McGill University and Genome Quebec, Innovation Centre, Montreal, QC, Canada) ,  Kerkhof Marjan (GRIAC research institute Groningen, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands) ,  Merid Simon Kebede (Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden) ,  van Rijkom Bianca (Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands) ,  Jankipersadsing Soesma A (Department of Pulmonology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands) ,  Jankipersadsing Soesma A (Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands) ,  Bonder Marc Jan (Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands) ,  Ballereau Stephane (European Institute for Systems Biology and Medicine, Campus Charles Merieux - Universite de Lyon, CIRI CNRS UMR5308, CNRS-ENS-UCBL-ENS, Lyon, France) ,  Ballereau Stephane (Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK) ,  Vermeulen Cornelis J (Department of Pulmonology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands) ,  Vermeulen Cornelis J (GRIAC research institute Groningen, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands) ,  Aguirre-Gamboa Raul (Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands) ,  de Jongste Johan C (Department of Pediatrics, Erasmus MC - Sophia Children’s Hospital University Medical Center, Rotterdam, The Netherlands) ,  Smit Henriette A (Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, the Netherlands) ,  Kumar Ashish (Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden) ,  Kumar Ashish (Department of Epidemiology and Public Health, Swiss Tropical and Public Health Institute, Basel, Switzerland) ,  Kumar Ashish (University of Basel, Basel, Switzerland) ,  Pershagen Goran (Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden) ,  Guerra Stefano (ISGlobal, Centre for Research in Environmental Epidemiology, the Barcelona Institute of Science and Technology, Barcelona, Spain) ,  Guerra Stefano (Asthma and Airway Disease Research Center, University of Arizona, Tucson, AZ, USA) ,  Garcia-Aymerich Judith (ISGlobal, Centre for Research in Environmental Epidemiology, the Barcelona Institute of Science and Technology, Barcelona, Spain) ,  Garcia-Aymerich Judith (Universitat Pompeu Fabra, Barcelona, Spain) ,  Garcia-Aymerich Judith (CIBER Epidemiologia y Salud Publica (CIBERESP), Madrid, Spain) ,  Greco Dario (Faculty of Medicine and Life Sciences and Institute of Biosciences and Medical Technology (BioMediTech), University of Tampere, Tampere, Finland) ,  Reinius Lovisa (Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden) ,  McEachan Rosemary R C (Bradford Institute for Health Research, Bradford Teaching Hospitals NHS Foundation Trust, Bradford, UK) ,  Azad Raf (Bradford Institute for Health Research, Bradford Teaching Hospitals NHS Foundation Trust, Bradford, UK) ,  Hovland Vegard (Department of Paediatrics, Oslo University Hospital, Oslo, Norway) ,  Mowinckel Petter (Department of Paediatrics, Oslo University Hospital, Oslo, Norway) ,  Alenius Harri (Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden) ,  Alenius Harri (Department of Bacteriology and Immunology, Medicum, University of Helsinki, Helsinki, Finland) ,  Fyhrquist Nanna (Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden) ,  Fyhrquist Nanna (Department of Bacteriology and Immunology, Medicum, University of Helsinki, Helsinki, Finland) ,  Lemonnier Nathanaeel (European Institute for Systems Biology and Medicine, Campus Charles Merieux - Universite de Lyon, CIRI CNRS UMR5308, CNRS-ENS-UCBL-ENS, Lyon, France) ,  Lemonnier Nathanaeel (Institute for Advanced Biosciences, UGA-INSERM U1209-CNRS UMR5309, Site Sante, Allee des Alpes, La Tronche, France) ,  Pellet Johann (European Institute for Systems Biology and Medicine, Campus Charles Merieux - Universite de Lyon, CIRI CNRS UMR5308, CNRS-ENS-UCBL-ENS, Lyon, France) ,  Auffray Charles (European Institute for Systems Biology and Medicine, Campus Charles Merieux - Universite de Lyon, CIRI CNRS UMR5308, CNRS-ENS-UCBL-ENS, Lyon, France) ,  van der Vlies Pieter (Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands) ,  van der Vlies Pieter (Research BV, Metslawier, the Netherlands) ,  van Diemen Cleo C (Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands) ,  Li Yang (Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands) ,  Wijmenga Cisca (Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands) ,  Netea Mihai G (Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, the Netherlands) ,  Moffatt Miriam F (National Heart and Lung Institute, Imperial College London, London, UK) ,  Cookson William O C M (National Heart and Lung Institute, Imperial College London, London, UK) ,  Anto Josep M (ISGlobal, Centre for Research in Environmental Epidemiology, the Barcelona Institute of Science and Technology, Barcelona, Spain) ,  Anto Josep M (Universitat Pompeu Fabra, Barcelona, Spain) ,  Anto Josep M (CIBER Epidemiologia y Salud Publica (CIBERESP), Madrid, Spain) ,  Anto Josep M (IMIM Hospital del Mar Medical Research Institute, Barcelona, Spain) ,  Bousquet Jean (University Hospital, Montpellier, France) ,  Bousquet Jean (Department of Dermatology, Charite, Berlin, Germany) ,  Laatikainen Tiina (National Institute for Health and Welfare, Helsinki, Finland) ,  Laatikainen Tiina (Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland) ,  Laprise Catherine (Universite du Quebec a Chicoutimi, Departement des sciences fondamentales, Saguenay, QC, Canada) ,  Laprise Catherine (Centre integre universitaire de sante et de services sociaux du Saguenay-Lac-Saint-Jean, 305 Saint-Vallier, Saguenay, QC, Canada) ,  Carlsen Kai-Hakon (Department of Paediatrics, Oslo University Hospital, Oslo, Norway) ,  Carlsen Kai-Hakon (Department of Paediatric and Adolescent Medicine, University of Oslo, Oslo, Norway) ,  Gori Davide (Department of Biomedical and Neuromotor sciences, University of Bologna, Bologna, Italy) ,  Porta Daniela (Department of Epidemiology Lazio Regional Health Service, Rome, Italy) ,  Iniguez Carmen (CIBER Epidemiologia y Salud Publica (CIBERESP), Madrid, Spain) ,  Iniguez Carmen (Epidemiology and Environmental Health Joint Research Unit, FISABIO-Universitat Jaume I-Universitat de Valencia, Valencia, Spain) ,  Bilbao Jose Ramon (Department of Genetics, Physical Anthropology and Animal Physiology, Biocruces Health Research Institute, CIBERDEM, University of the Basque Country UPV-EHU, Leioa-Bizkaia, Spain) ,  Kogevinas Manolis (ISGlobal, Centre for Research in Environmental Epidemiology, the Barcelona Institute of Science and Technology, Barcelona, Spain) ,  Kogevinas Manolis (CIBER Epidemiologia y Salud Publica (CIBERESP), Madrid, Spain) ,  Wright John (Bradford Institute for Health Research, Bradford Teaching Hospitals NHS Foundation Trust, Bradford, UK) ,  Brunekreef Bert (Institute for Risk Assessment Sciences, Utrecht University, the Netherlands) ,  Brunekreef Bert (Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, the Netherlands) ,  Kere Juha (Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden) ,  Kere Juha (Department of Medical and Molecular Genetics, King’s College London, London, UK) ,  Nawijn Martijn C (GRIAC research institute Groningen, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands) ,  Nawijn Martijn C (Department of Pathology and Medical Biology, Experimental Pulmonology and Inflammation Research, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands) ,  Annesi-Maesano Isabella (Epidemiology of Allergic and Respiratory Diseases Department (EPAR), Sorbonne Universite, INSERM, Pierre Louis Institute of Epidemiology and Public Health, Saint-Antoine Medical School, Paris, France) ,  Sunyer Jordi (ISGlobal, Centre for Research in Environmental Epidemiology, the Barcelona Institute of Science and Technology, Barcelona, Spain) ,  Sunyer Jordi (Universitat Pompeu Fabra, Barcelona, Spain) ,  Sunyer Jordi (CIBER Epidemiologia y Salud Publica (CIBERESP), Madrid, Spain) ,  Sunyer Jordi (IMIM Hospital del Mar Medical Research Institute, Barcelona, Spain) ,  Melen Erik (Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden) ,  Melen Erik (Sachs Children’s Hospital, Stockholm, Sweden) ,  Melen Erik (Centre for Occupational and Environmental Medicine, Stockholm County Council, Stockholm, Sweden) ,  Koppelman Gerard H (GRIAC research institute Groningen, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands) ,  Koppelman Gerard H (Department of Pediatric Pulmonology and Pediatric Allergy, Beatrix Children’s Hospital, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands)
資料名： Lancet Respiratory Medicine  (Lancet Respiratory Medicine)
巻： 6  号： 5  ページ： 379-388  発行年： 2018年 
JST資料番号： W3111A  ISSN： 2213-2600  資料種別： 逐次刊行物 (A)
記事区分： 原著論文  発行国： オランダ (NLD)  言語： 英語 (EN)

抄録/ポイント： 小児喘息に関連するDNAメチル化プロフィールは,疾患病因に新しい洞察を提供する可能性がある。小児喘息に関連するメチル化プロファイルを評価するために,エピゲノム関連研究を行った。アレルギー(MeDALL)プロジェクトの開発の機構の中で大規模なエピゲノム関連研究(EWAS)を行った。喘息患者207名および年齢4~5歳の対照者610名,および横断的な症例対照デザインを用いて喘息患者185名および年齢8歳の対照者546名の全血において,Illina Infiniumヒトメチル化450BeadChips(450K)を用いてエピゲノムメチル化を検討した。発見分析における異なるメチル化CpG部位の同定後,6つの追加ヨーロッパコホートからの子供(4~16歳;247症例と2949対照)における検証研究を行い,結果をメタ分析した。次に,臍帯血中の複製CpG部位が1316人の小児において後期喘息を予測するかどうかを検討した。続いて,好酸球および呼吸上皮細胞における同定されたCpG部位の細胞型特異的メチル化およびそれらの関連遺伝子発現特徴を検討した。16歳の小児の鼻ブラッシングと血液好酸球から分離したDNA(喘息患者16名,年齢2~56歳)における複製CpG部位の喘息関連の細胞型特異性を研究し,喘息患者74名と対照者93名(年齢1~79歳)の全血DNAサンプルと比較した。複製CpG部位に関連する全血転写プロファイルを蛍光活性化細胞選別により選別した末梢血単核細胞のサブセットのRNA-seqデータを用いて注釈した。27のメチル化CpG部位を発見分析で同定した。これらのCpG部位のうち14は複製され,メタ分析後にゲノム全体の有意性(p<1,14×10~7)を通過した。一貫して低いメチル化レベルは,喘息を有する参加者において4歳から16歳までの小児期にわたるすべての関連遺伝子座において観察されたが,出生時の臍帯血においては観察されなかった。全14CpG部位は全血DNAを用いた第2複製研究において喘息と有意に関連し,精製好酸球における喘息と強く関連していた。これらのCpG部位に関連する全血転写特性は,好酸球,エフェクタおよびメモリーCD8T細胞およびナチュラルキラー細胞の活性化の増加,およびナイーブT細胞の数の減少を示した。14のCpG部位のうちの5つは,呼吸上皮細胞における喘息と関連し,交差組織後成的効果を示した。出生後に得られた14のCpG部位における全血DNAメチル化の低下は,小児喘息と強く関連していた。これらのCpG部位およびそれらの関連する転写プロファイルは,小児喘息における好酸球および細胞傷害性T細胞の活性化を示す。著者らの知見は,臨床的状況におけるepiティクスの役割のさらなる研究に価値がある。EUと第17の枠組みプログラム(MeDALLプロジェクト)。Copyright 2018 Elsevier B.V., Amsterdam. All rights reserved. Translated from English into Japanese by JST.【JST・京大機械翻訳】

シソーラス用語： *DNA【核酸】 ,  *メチル化 ,  子供 ,  *ゲノム ,  上皮細胞 ,  臍帯血 ,  好酸球 ,  *喘息 ,  ヒト ,  遺伝子発現 ,  患者 ,  病因
準シソーラス用語： CpG ,  *DNAメチル化 ,  *小児喘息 , 【Automatic Indexing@JST】

分類 (1件)： 分子遺伝学一般  (EC02010J)

タイトルに関連する用語 (4件)： 小児喘息 ,  DNAメチル化 ,  エピゲノム ,  メタ分析