生物谷综合:不宁腿综合征(RLS)患者往往都会抱怨,腿像针扎一样疼,并且经常会突然起身行走,为的是缓解这种不适,每到夜晚,还要忍受不自觉的腿部痉挛,科学家将其称为周期性腿动。曾有人怀疑RLS并不是一种真正的疾病。如今,两项独立研究发现,某些基因与这种折磨存在联系。
科学家对RLS的流行广度以及种族差异进行了评估:一项研究发现,每1000名新加坡人中就有1人罹患该病,而另一项研究则指出,在西欧,将近15%的人正在遭受RLS的折磨。然而无论哪种比率,其症状通常都会在夜晚变得更加严重,甚至中断睡眠,影响人们的生活质量。研究人员同时发现,这种疾病还与高血压存在一定的联系。但有些怀疑论者则表示,制药公司总在夸大RLS的危害,以致于产生过度诊断。
由德国慕尼黑市人类遗传学研究所和马普学会精神病学研究所的Juliane Winkelmann领导的一个研究小组,对具有“不宁腿”家族史的401名患者进行了调查。研究人员分析了受试者脱氧核糖核酸(DNA)中的50万种单氨基酸变异或单核苷酸多态性,旨在寻找其共性。他们最终在对德国人和法裔加拿大人进行的两项独立研究中证实了可能的罪魁祸首。在最新出版的《自然—遗传学》杂志中,研究人员描述了与RLS症状相关的3种变异。不同寻常的是,这些基因与胚胎发育有关。Winkelmann说:“我们感到非常惊讶。”
无独有偶,由冰岛雷克雅未克市deCODE遗传学——一家生物制药公司——的遗传学家Hreinn Stefansson领导的研究小组,对17000名冰岛人的基因序列进行了分析,其中有965人患有RLS。研究人员发现了一种名为BTBD9的基因——它同时发现于有关德国人的研究中。与正常人相比,携带这种基因的人出现RLS症状的几率增加了80%。BTBD9能够解释50%的RLS病例,研究小组在本周的《新英格兰医学杂志》(NEJM)上报告了这一研究成果。研究小组成员之一、该公司首席执行官Kari Stefansson表示:“这一基因的发现表明RLS的发生无疑有其生物学背景。”研究人员同时发现,RLS与低水平的铁和多巴胺有直接关系。
美国马萨诸塞州波士顿市哈佛医学院的睡眠专家John Winkelman表示:“我们如今找到了一条线索,表明遗传学因素可能是导致RLS的部分原因。”他同时指出,周期性腿动也会出现在其他睡眠紊乱中,Winkelman很想知道,这些变异是否也存在于这些疾病的患者中。(引自科学时报)
原始出处(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: janew@mpipsykl.mpg.de
Correspondence to: Thomas Meitinger1,3,16 e-mail: meitinger@gsf.de