生物谷：德国研究人员日前发现，一种名为“ＡＢＣＧ８”的基因发生变异可使人患胆结石的风险增加一倍。
据德国媒体报道，基尔大学研究人员约亨·汉普领导的科研小组发现，胆结石主要是由于胆汁中胆固醇或非结合胆红素的含量过多造成，而“ＡＢＣＧ８”基因控制着肝脏向胆道排放胆固醇的过程。该基因的变异导致排放进入胆道的胆固醇过多，从而导致胆结石风险增大。
不过，研究人员指出，虽然该基因与胆结石有一定关系，但过度肥胖仍是与胆结石相关的最大健康威胁。胆结石是发达国家中的常见疾病，发病率达１０％至２０％。
该研究发表在英国《自然遗传学》杂志网站上。（新华网）
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
