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ヨーロッパ系の人における特発性肺線維症に対する感受性と関連する遺伝的変異:全ゲノム関連研究【Powered by NICT】

Genetic variants associated with susceptibility to idiopathic pulmonary fibrosis in people of European ancestry: a genome-wide association study

著者 (67件)： Allen Richard J (Department of Health Sciences, University of Leicester, Leicester, UK) ,  Porte Joanne (Division of Respiratory Medicine, University of Nottingham, Nottingham, UK) ,  Porte Joanne (National Institute for Health Research, Nottingham Biomedical Research Centre, Nottingham University Hospitals, Nottingham, UK) ,  Porte Joanne (Nottingham Molecular Pathology Node, University of Nottingham, Nottingham, UK) ,  Braybrooke Rebecca (National Institute for Health Research, Nottingham Biomedical Research Centre, Nottingham University Hospitals, Nottingham, UK) ,  Braybrooke Rebecca (Division of Epidemiology and Public Health, University of Nottingham, Nottingham, UK) ,  Flores Carlos (Research Unit, Hospital Universitario NS de Candelaria, Universidad de La Laguna, Santa Cruz de Tenerife, Spain) ,  Flores Carlos (CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III, Spain) ,  Flores Carlos (Instituto Tecnologico y de Energias Renovables (ITER, S.A.), Santa Cruz de Tenerife, Spain) ,  Fingerlin Tasha E (Center for Genes, Environment and Health, National Jewish Health, Denver, CO, USA) ,  Fingerlin Tasha E (Department of Biostatistics and Informatics, University of Colorado, Denver, CO, USA) ,  Oldham Justin M (Department of Internal Medicine, University of California Davis, Davis, CA, USA) ,  Guillen-Guio Beatriz (Research Unit, Hospital Universitario NS de Candelaria, Universidad de La Laguna, Santa Cruz de Tenerife, Spain) ,  Ma Shwu-Fan (Section of Pulmonary and Critical Care Medicine, University of Chicago, Chicago, IL, USA) ,  Okamoto Tsukasa (Department of Medicine, University of Colorado Denver, Denver, CO, USA) ,  John Alison E (Division of Respiratory Medicine, University of Nottingham, Nottingham, UK) ,  John Alison E (National Institute for Health Research, Nottingham Biomedical Research Centre, Nottingham University Hospitals, Nottingham, UK) ,  Obeidat Ma’en (The University of British Columbia Centre for Heart Lung Innovation, St Paul’s Hospital, Vancouver, BC, Canada) ,  Yang Ivana V (Center for Genes, Environment and Health, National Jewish Health, Denver, CO, USA) ,  Yang Ivana V (Department of Medicine, University of Colorado Denver, Denver, CO, USA) ,  Henry Amanda (Division of Respiratory Medicine, University of Nottingham, Nottingham, UK) ,  Henry Amanda (National Institute for Health Research, Nottingham Biomedical Research Centre, Nottingham University Hospitals, Nottingham, UK) ,  Hubbard Richard B (National Institute for Health Research, Nottingham Biomedical Research Centre, Nottingham University Hospitals, Nottingham, UK) ,  Hubbard Richard B (Division of Epidemiology and Public Health, University of Nottingham, Nottingham, UK) ,  Navaratnam Vidya (National Institute for Health Research, Nottingham Biomedical Research Centre, Nottingham University Hospitals, Nottingham, UK) ,  Navaratnam Vidya (Division of Epidemiology and Public Health, University of Nottingham, Nottingham, UK) ,  Saini Gauri (Division of Respiratory Medicine, University of Nottingham, Nottingham, UK) ,  Saini Gauri (National Institute for Health Research, Nottingham Biomedical Research Centre, Nottingham University Hospitals, Nottingham, UK) ,  Thompson Norma (Division of Respiratory Medicine, University of Nottingham, Nottingham, UK) ,  Thompson Norma (National Institute for Health Research, Nottingham Biomedical Research Centre, Nottingham University Hospitals, Nottingham, UK) ,  Booth Helen L (Department of Thoracic Medicine, University College London Hospitals, London, UK) ,  Hart Simon P (Respiratory Research Group, Centre for Cardiovascular and Metabolic Research, The Hull York Medical School, Hull, UK) ,  Hill Mike R (Clinical Trial Service Unit & Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK) ,  Hirani Nik (MRC Centre for Inflammation Research at the University of Edinburgh, Edinburgh, UK) ,  Maher Toby M (NIHR Respiratory Biomedical Research Unit, Royal Brompton Hospital, London, UK) ,  Maher Toby M (Fibrosis Research Group, Inflammation, Repair and Development Section, National Heart and Lung Institute, Imperial College, London, UK) ,  McAnulty Robin J (UCL Respiratory Centre for Inflammation and Tissue Repair, University College London, London, UK) ,  Millar Ann B (Academic Respiratory Unit, School of Clinical Sciences, University of Bristol, Bristol, UK) ,  Molyneaux Philip L (NIHR Respiratory Biomedical Research Unit, Royal Brompton Hospital, London, UK) ,  Molyneaux Philip L (Fibrosis Research Group, Inflammation, Repair and Development Section, National Heart and Lung Institute, Imperial College, London, UK) ,  Parfrey Helen (Respiratory Medicine, Papworth Hospital, Cambridge, UK) ,  Rassl Doris M (Department of Pathology, Papworth Hospital, Cambridge, UK) ,  Whyte Moira K B (MRC Centre for Inflammation Research at the University of Edinburgh, Edinburgh, UK) ,  Fahy William A (Fibrosis Discovery Performance Unit, GlaxoSmithKline, Stevenage, UK) ,  Marshall Richard P (Fibrosis Discovery Performance Unit, GlaxoSmithKline, Stevenage, UK) ,  Oballa Eunice (Fibrosis Discovery Performance Unit, GlaxoSmithKline, Stevenage, UK) ,  Bosse Yohan (Institut Universitaire de Cardiologie et de Pneumologie de Quebec, Department of Molecular Medicine, Laval University, Quebec City, QC, Canada) ,  Nickle David C (Merck Research Laboratories, Genetics and Pharmacogenomics, Boston, MA, USA) ,  Sin Don D (The University of British Columbia Centre for Heart Lung Innovation, St Paul’s Hospital, Vancouver, BC, Canada) ,  Sin Don D (Respiratory Division, Department of Medicine, University of British Columbia, Vancouver, BC, Canada) ,  Timens Wim (Department of Pathology and Medical Biology, University Medical Centre Groningen, Groningen Research Institute for Asthma and COPD, University of Groningen, Groningen, Netherlands) ,  Shrine Nick (Department of Health Sciences, University of Leicester, Leicester, UK) ,  Sayers Ian (Division of Respiratory Medicine, University of Nottingham, Nottingham, UK) ,  Sayers Ian (National Institute for Health Research, Nottingham Biomedical Research Centre, Nottingham University Hospitals, Nottingham, UK) ,  Hall Ian P (Division of Respiratory Medicine, University of Nottingham, Nottingham, UK) ,  Hall Ian P (National Institute for Health Research, Nottingham Biomedical Research Centre, Nottingham University Hospitals, Nottingham, UK) ,  Noth Imre (Section of Pulmonary and Critical Care Medicine, University of Chicago, Chicago, IL, USA) ,  Schwartz David A (Center for Genes, Environment and Health, National Jewish Health, Denver, CO, USA) ,  Schwartz David A (Department of Medicine, University of Colorado Denver, Denver, CO, USA) ,  Schwartz David A (Department of Immunology, University of Colorado Denver, Denver, CO, USA) ,  Tobin Martin D (Department of Health Sciences, University of Leicester, Leicester, UK) ,  Tobin Martin D (National Institute for Health Research, Leicester Respiratory Biomedical Research Centre, Glenfield Hospital, Leicester, UK) ,  Wain Louise V (Department of Health Sciences, University of Leicester, Leicester, UK) ,  Wain Louise V (National Institute for Health Research, Leicester Respiratory Biomedical Research Centre, Glenfield Hospital, Leicester, UK) ,  Jenkins R Gisli (Division of Respiratory Medicine, University of Nottingham, Nottingham, UK) ,  Jenkins R Gisli (National Institute for Health Research, Nottingham Biomedical Research Centre, Nottingham University Hospitals, Nottingham, UK) ,  Jenkins R Gisli (Nottingham Molecular Pathology Node, University of Nottingham, Nottingham, UK)
資料名： Lancet Respiratory Medicine  (Lancet Respiratory Medicine)
巻： 5  号： 11  ページ： 869-880  発行年： 2017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： 特発性肺線維症(IPF)は高い死亡率,原因不明,といくつかの治療選択肢と慢性進行性肺疾患である。研究はIPFの開発と関連する重要な遺伝的リスクを同定した;が,遺伝的危険因子はIPFを促進する機構は不明のままである。IPF感受性と関連した遺伝的変異体を同定し,遺伝子および蛋白質発現解析を用いた機構的洞察を提供することを目的とした。2段階アプローチ:英国における九種類の中心から募集したヨーロッパ系のIPFと年齢,性別および喫煙状況を対応英国バイオバンク(ステージ1)から選択された対照患者におけるゲノムワイド関連研究を用いた;シカゴコンソーシアムからの二つの独立したUS試料とコロラドコンソーシアム(ステージ2)からIPF患者および対照者の独立データセットにおいて関連する遺伝的変異体のフォローアップ。大きなトランスクリプトームおよびゲノムデータ資源における遺伝子発現に対する新たな信号の影響を調べ,IPFと対照患者からの肺組織試料を用いた発現を検討した。IPF患者602名および対照3366名はステージ1のために選択した。ステージ2では,IPFの2158患者及び5195対照を選択した。Aキナーゼアンカー蛋白質13(AKAP13;rs62025270,オッズ比[OR]127[95%CI118 137],P=132×10~ 9)近くのIPF感受性との関連の新しいゲノムワイド有意な信号を同定し,以前に報告された信号,ムチンにおける5b(MUC5B;rs35705950,OR289[256 326],P=112×10~66)とデスモプラキン(D SP;rs2076295,OR144[135 154],P=781×10~ 28)を含むことを確認した。rs62025270では,IPFに対する感受性の増加に関連する対立遺伝子Aはまた,肺切除手順(n=1111)を受けた患者からの肺組織におけるAKAP13mRNAの発現増加と関連していた。AKAP13はIPF患者の肺胞上皮とリンパろ胞で発現していることを示し,AKAP13mRNA発現は,対照(n=51)から肺組織よりもIPF(n=46)患者からの肺組織で142倍高かった。AKAP13はRhoAの活性化を調節するRhoグアニンヌクレオチド交換因子,線維芽細胞促進性シグナル伝達経路に関与することが知られている。IPFに対する感受性遺伝子としてAKAP13の同定は,IPF患者におけるRhoA経路阻害剤を標的とする成功の可能性を増加した。英国医学研究審議会,国立心臓,肺および血液研究所米国国立衛生研究所,Agenciaカナリア島のde Investigacion,Innovacion y SociedadのInformacion,スペイン,英国国立衛生研究所研究と英国肺財団。Copyright 2017 Elsevier B.V., Amsterdam. All rights reserved. Translated from English into Japanese by JST.【Powered by NICT】

シソーラス用語： 肺疾患 ,  遺伝子発現 ,  *ゲノム ,  心臓 ,  患者 ,  *感受性 ,  喫煙 ,  線維芽細胞 ,  対立遺伝子 ,  死亡率 ,  英国
準シソーラス用語： 肺組織 ,  蛋白質発現 ,  *遺伝的変異 ,  *特発性肺線維症 , 【Automatic Indexing@JST】

分類 (1件)： 呼吸器の疾患  (GI03000Z)

タイトルに関連する用語 (7件)： ヨーロッパ ,  人 ,  特発性肺線維症 ,  感受性 ,  遺伝的変異 ,  ゲノム ,  研究