生物谷綜合：不寧腿綜合征(RLS)患者往往都會(huì)抱怨,，腿像針扎一樣疼,，并且經(jīng)常會(huì)突然起身行走，為的是緩解這種不適,，每到夜晚,，還要忍受不自覺的腿部痙攣，科學(xué)家將其稱為周期性腿動(dòng),。曾有人懷疑RLS并不是一種真正的疾病,。如今,，兩項(xiàng)獨(dú)立研究發(fā)現(xiàn)，某些基因與這種折磨存在聯(lián)系,。
科學(xué)家對(duì)RLS的流行廣度以及種族差異進(jìn)行了評(píng)估：一項(xiàng)研究發(fā)現(xiàn),，每1000名新加坡人中就有1人罹患該病，而另一項(xiàng)研究則指出,，在西歐,，將近15%的人正在遭受RLS的折磨,。然而無論哪種比率,，其癥狀通常都會(huì)在夜晚變得更加嚴(yán)重，甚至中斷睡眠,，影響人們的生活質(zhì)量,。研究人員同時(shí)發(fā)現(xiàn)，這種疾病還與高血壓存在一定的聯(lián)系,。但有些懷疑論者則表示,，制藥公司總在夸大RLS的危害，以致于產(chǎn)生過度診斷,。
由德國(guó)慕尼黑市人類遺傳學(xué)研究所和馬普學(xué)會(huì)精神病學(xué)研究所的Juliane Winkelmann領(lǐng)導(dǎo)的一個(gè)研究小組,，對(duì)具有“不寧腿”家族史的401名患者進(jìn)行了調(diào)查。研究人員分析了受試者脫氧核糖核酸（DNA）中的50萬種單氨基酸變異或單核苷酸多態(tài)性,，旨在尋找其共性,。他們最終在對(duì)德國(guó)人和法裔加拿大人進(jìn)行的兩項(xiàng)獨(dú)立研究中證實(shí)了可能的罪魁禍?zhǔn)住Ｔ谧钚鲁霭娴摹蹲匀?mdash;遺傳學(xué)》雜志中,，研究人員描述了與RLS癥狀相關(guān)的3種變異,。不同尋常的是，這些基因與胚胎發(fā)育有關(guān),。Winkelmann說：“我們感到非常驚訝,。”
無獨(dú)有偶，由冰島雷克雅未克市deCODE遺傳學(xué)——一家生物制藥公司——的遺傳學(xué)家Hreinn Stefansson領(lǐng)導(dǎo)的研究小組,，對(duì)17000名冰島人的基因序列進(jìn)行了分析,，其中有965人患有RLS。研究人員發(fā)現(xiàn)了一種名為BTBD9的基因——它同時(shí)發(fā)現(xiàn)于有關(guān)德國(guó)人的研究中,。與正常人相比,，攜帶這種基因的人出現(xiàn)RLS癥狀的幾率增加了80%。BTBD9能夠解釋50%的RLS病例,，研究小組在本周的《新英格蘭醫(yī)學(xué)雜志》（NEJM）上報(bào)告了這一研究成果,。研究小組成員之一、該公司首席執(zhí)行官Kari Stefansson表示：“這一基因的發(fā)現(xiàn)表明RLS的發(fā)生無疑有其生物學(xué)背景,。”研究人員同時(shí)發(fā)現(xiàn),，RLS與低水平的鐵和多巴胺有直接關(guān)系,。
美國(guó)馬薩諸塞州波士頓市哈佛醫(yī)學(xué)院的睡眠專家John Winkelman表示：“我們?nèi)缃裾业搅艘粭l線索，表明遺傳學(xué)因素可能是導(dǎo)致RLS的部分原因,。”他同時(shí)指出,，周期性腿動(dòng)也會(huì)出現(xiàn)在其他睡眠紊亂中，Winkelman很想知道,，這些變異是否也存在于這些疾病的患者中,。（引自科學(xué)時(shí)報(bào)）
原始出處（一）:
Nature Genetics
Published online: 18 July 2007 | doi:10.1038/ng2099
Genome-wide association study of restless legs syndrome identifies common variants in three genomic regions
Juliane Winkelmann1,2,3, Barbara Schormair1,3, Peter Lichtner1,3, Stephan Ripke2, Lan Xiong4, Shapour Jalilzadeh1,3, Stephany Fulda2, Benno Pütz2, Gertrud Eckstein1,3, Stephanie Hauk1,3, Claudia Trenkwalder5, Alexander Zimprich6, Karin Stiasny-Kolster7, Wolfgang Oertel7, Cornelius G Bachmann8, Walter Paulus8, Ines Peglau9, Ilonka Eisensehr10, Jacques Montplaisir11,12, Gustavo Turecki13, Guy Rouleau4, Christian Gieger14, Thomas Illig14, H-Erich Wichmann14,15, Florian Holsboer2, Bertram Müller-Myhsok2,16 & Thomas Meitinger1,3,16
Restless legs syndrome (RLS) is a frequent neurological disorder characterized by an imperative urge to move the legs during night, unpleasant sensation in the lower limbs, disturbed sleep and increased cardiovascular morbidity. In a genome-wide association study we found highly significant associations between RLS and intronic variants in the homeobox gene MEIS1, the BTBD9 gene encoding a BTB(POZ) domain as well as variants in a third locus containing the genes encoding mitogen-activated protein kinase MAP2K5 and the transcription factor LBXCOR1 on chromosomes 2p, 6p and 15q, respectively. Two independent replications confirmed these association signals. Each genetic variant was associated with a more than 50% increase in risk for RLS, with the combined allelic variants conferring more than half of the risk. MEIS1 has been implicated in limb development, raising the possibility that RLS has components of a developmental disorder.
Institute of Human Genetics, GSF National Research Center of Environment and Health, D-85764 Neuherberg, Munich, Germany.
Max Planck Institute of Psychiatry, D-80804 Munich, Germany.
Technical University, Institute of Human Genetics, D-81675 Munich, Germany.
Laboratoire d'étude des maladies du cerveau, Centre de recherche du CHUM, Hôpital Notre-Dame, Université de Montréal, Montréal, Québec H2L 4M1, Canada.
Paracelsus-Elena-Hospital, 34128 Kassel, Germany.
Neurological Department, Medical University of Vienna, 1090 Vienna, Austria.
Philipps University Marburg, Department of Neurology, 35039 Marburg, Germany.
University of Göttingen, Department of Clinical Neurophysiology, 37070 Göttingen, Germany.
Neurologische Praxis, 10969 Berlin, Germany.
Neurologische Praxis Sendlingerstrasse, 80331 Munich, Germany.
Centre d'étude du sommeil, Hôpital du Sacré-Cur de Montréal, Montréal, Québec H4J 1C5, Canada.
Centre de recherche en sciences neurologiques, Université de Montréal, Montréal, Québec H4J 1C5, Canada.
Departments of Psychiatry and Human Genetics, McGill University, Douglas Hospital, Montreal, Quebec H4H 1R3, Canada.
Institute of Epidemiology, GSF National Research Center for Environment and Health, 85764 Neuherberg, Munich, Germany.
Institute of Medical Informatics, Biometry and Epidemiology, Ludwig-Maximilians-Universität, 81377 Munich, Germany.
These authors contributed equally to this work.
Correspondence to: Juliane Winkelmann1,2,3 e-mail: [email protected]
Correspondence to: Thomas Meitinger1,3,16 e-mail: [email protected]
