生物谷報(bào)道：科學(xué)家最近找到一種基因,，它會(huì)使兒童患哮喘的風(fēng)險(xiǎn)增加６０％至７０％。新發(fā)現(xiàn)可能有助于開發(fā)治療兒童哮喘的新型靶向藥物,。
美,、英、法,、德等國(guó)科學(xué)家在新一期《自然》雜志上報(bào)告說,，他們對(duì)２０００多名兒童進(jìn)行了研究，研究對(duì)象中的９９４人為哮喘患者,，１２４３人沒有患哮喘,。科學(xué)家以這些兒童為對(duì)象,，分析了組成ＤＮＡ（脫氧核糖核酸）的核苷酸的變異情況,。
在分析了３０多萬(wàn)個(gè)變異核苷酸分子后，科學(xué)家發(fā)現(xiàn)一種名為ＯＲＭＤＬ３的基因與兒童哮喘發(fā)作“高度相關(guān)”,。分析顯示,，攜帶這種基因的兒童患哮喘的概率要比普通兒童高６０％至７０％。
科學(xué)家稱,，這是迄今發(fā)現(xiàn)的有關(guān)兒童哮喘的最強(qiáng)有力的基因證據(jù),。他們計(jì)劃下一步開展更大規(guī)模研究，尋找其他與兒童哮喘相關(guān)的基因,，并希望將來能夠開發(fā)出以這些基因?yàn)榘邢虻闹委焹和幬铩?/p>
原始出處:
Nature advance online publication 4 July 2007 | doi:10.1038/nature06014; Received 24 April 2007; Accepted 14 June 2007; Published online 4 July 2007
Genetic variants regulating ORMDL3 expression contribute to the risk of childhood asthma
Miriam F. Moffatt1,16, Michael Kabesch2,16, Liming Liang3,16, Anna L. Dixon4, David Strachan5, Simon Heath6, Martin Depner2, Andrea von Berg7, Albrecht Bufe8, Ernst Rietschel9, Andrea Heinzmann10, Burkard Simma11, Thomas Frischer12, Saffron A. G. Willis-Owen1, Kenny C. C. Wong1, Thomas Illig13, Christian Vogelberg14, Stephan K. Weiland15, Erika von Mutius2, Gonçalo R. Abecasis3, Martin Farrall4, Ivo G. Gut6, G. Mark Lathrop6 & William O. C. Cookson1
National Heart and Lung Institute, Imperial College, London SW3 6LY, UK
University Children's Hospital, Ludwig Maximilians University, D80337 Munich, Germany
Center for Statistical Genetics, Department of Biostatistics, SPH II, Ann Arbor, Michigan 48109-2029, USA
Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK
Division of Community Health Science, St George's, University of London, London SW17 0RE, UK
Centre National de Génotypage, Institut Génomique, Commissariat à l'Énergie Atomique, 91057 Evry, France
Research Institute for the Prevention of Allergic Diseases, Children's Department, Marien-Hospital, D46483 Wesel, Germany
Department of Experimental Pneumology, Ruhr-University, D44789 Bochum, Germany
University Children's Hospital, University of Cologne, D50924 Cologne, Germany
University Children's Hospital, Albert Ludwigs University, D79106 Freiburg, Germany
Children's Department, Feldkirch Hospital, A6800 Feldkirch, Austria
University Children's Hospital Vienna, A1090 Vienna, Austria
Institute of Epidemiology, GSF-Research Centre for Environment and Health, D85764 Neuherberg, Germany
University Children's Hospital, Technical University Dresden, D01307 Dresden, Germany
Institute of Epidemiology, Ulm University, D89081 Germany
These authors contributed equally to this work.
Correspondence to: William O. C. Cookson1 Correspondence and requests for materials should be addressed to W.O.C.C. (Email: [email protected]).
Asthma is caused by a combination of poorly understood genetic and environmental factors1, 2. We have systematically mapped the effects of single nucleotide polymorphisms (SNPs) on the presence of childhood onset asthma by genome-wide association. We characterized more than 317,000 SNPs in DNA from 994 patients with childhood onset asthma and 1,243 non-asthmatics, using family and case-referent panels. Here we show multiple markers on chromosome 17q21 to be strongly and reproducibly associated with childhood onset asthma in family and case-referent panels with a combined P value of P < 10-12. In independent replication studies the 17q21 locus showed strong association with diagnosis of childhood asthma in 2,320 subjects from a cohort of German children (P = 0.0003) and in 3,301 subjects from the British 1958 Birth Cohort (P = 0.0005). We systematically evaluated the relationships between markers of the 17q21 locus and transcript levels of genes in Epstein–Barr virus (EBV)-transformed lymphoblastoid cell lines from children in the asthma family panel used in our association study. The SNPs associated with childhood asthma were consistently and strongly associated (P < 10-22) in cis with transcript levels of ORMDL3, a member of a gene family that encodes transmembrane proteins anchored in the endoplasmic reticulum3. The results indicate that genetic variants regulating ORMDL3 expression are determinants of susceptibility to childhood asthma.
