生物谷综合:胆结石是工业化国家中最普遍的健康问题,它会导致器官的损害或感染,目前,世界上有10%~20%的人患此病。研究人员在7月在线出版的《自然—遗传学》上报告说,肝脏中一个胆固醇运输者的编码基因的变异会导致胆固醇的患病风险增加2倍。
科学家们早已知道,胆结石的易患性受遗传因素的影响,但鉴别这些遗传影响因子的研究进展则极为缓慢。Jochen Hampe和同事对德国两组人群进行了大范围的基因相关性研究,同时还跟踪德国和智利患此疾病的人群。他们发现,单个的基因变异能够改变肝脏的一种胆固醇运输者ABCG8序列,从而认为这种基因的变异与胆结石病有关。
胆汁是由肝脏产生的,并储存在胆囊中,当身体需要消化脂肪时,它就会从胆囊中释放出来。而当胆固醇或胆红素等胆汁成分水平升高并变成石头时,胆结石就发生了,因此,切除胆囊是目前治疗胆结石最常用的方法。新研究认为ABCG8的变异促进更多的胆固醇转化为胆汁。(援引科学时报)
原始出处:
Nature Genetics
Published online: 15 July 2007 | doi:10.1038/ng2101
A genome-wide association scan identifies the hepatic cholesterol transporter ABCG8 as a susceptibility factor for human gallstone disease
Stephan Buch1,2,3,13, Clemens Schafmayer3,4,13, Henry Völzke5, Christian Becker6,7, Andre Franke2, Huberta von Eller-Eberstein3, Christian Kluck6,7, Ingelore Bässmann6,7, Mario Brosch1, Frank Lammert8, Juan Francisco Miquel9, Flavio Nervi9, Michael Wittig2, Dieter Rosskopf10, Birgit Timm3, Christine Höll3, Marcus Seeger1, Abdou ElSharawy2, Tim Lu11, Jan Egberts4, Fred Fändrich4, Ulrich R Fölsch1, Michael Krawczak3,11, Stefan Schreiber2,3, Peter Nürnberg6,12, Jürgen Tepel4 & Jochen Hampe1
Abstract
With an overall prevalence of 10–20%, gallstone disease (cholelithiasis) represents one of the most frequent and economically relevant health problems of industrialized countries1, 2. We performed an association scan of >500,000 SNPs in 280 individuals with gallstones and 360 controls. A follow-up study of the 235 most significant SNPs in 1,105 affected individuals and 873 controls replicated the disease association of SNP A-1791411 in ABCG8 (allelic P value PCCA = 4.1 10-9), which was subsequently attributed to coding variant rs11887534 (D19H). Additional replication was achieved in 728 German (P = 2.8 10-7) and 167 Chilean subjects (P = 0.02). The overall odds ratio for D19H carriership was 2.2 (95% confidence interval: 1.8–2.6, P = 1.4 10-14) in the full German sample. Association was stronger in subjects with cholesterol gallstones (odds ratio = 3.3), suggesting that His19 might be associated with a more efficient transport of cholesterol into the bile.
First Department of Medicine, University Hospital Schleswig-Holstein, 24105 Kiel, Germany.
Institute for Clinical Molecular Biology, University Hospital Schleswig-Holstein, 24105 Kiel, Germany.
POPGEN Biobank, University Hospital Schleswig-Holstein, 24105 Kiel, Germany.
Department of General and Thoracic Surgery, University Hospital Schleswig-Holstein, 24105 Kiel, Germany.
Institute for Community Medicine, University Hospital Greifswald, Walther Rathenau Str. 48, 17487 Greifswald, Germany.
Cologne Center for Genomics, University of Cologne, Zülpicher Strasse 47, 50674 Cologne, Germany.
RZPD German Resource Center for Genome Research, Heubnerweg 6, 14059 Berlin, Germany.
Department of Internal Medicine I, University Hospital Bonn, Sigmund Freud-Strasse 25, 53105 Bonn, Germany.
Departamento de Gastroenterologia, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile.
Institute of Pharmacology, Ernst-Moritz-Arndt University Greifswald, Friedrich Loeffler Str. 23d, 17487 Greifswald, Germany.
Institute of Medical Statistics and Informatics, University Hospital Schleswig-Holstein, 24105 Kiel, Germany.
Center for Molecular Medicine Cologne (CMMC), University of Cologne, Joseph-Stelzmann-Strasse 52, 50931 Köln, Germany.
These authors contributed equally to this work.
Correspondence to: Jochen Hampe1 e-mail: jhampe@1med.uni-kiel.de