生物谷綜合：膽結(jié)石是工業(yè)化國家中最普遍的健康問題,，它會導(dǎo)致器官的損害或感染，目前,，世界上有10%～20%的人患此病,。研究人員在7月在線出版的《自然—遺傳學(xué)》上報告說，肝臟中一個膽固醇運輸者的編碼基因的變異會導(dǎo)致膽固醇的患病風(fēng)險增加2倍,。
科學(xué)家們早已知道,，膽結(jié)石的易患性受遺傳因素的影響，但鑒別這些遺傳影響因子的研究進(jìn)展則極為緩慢,。Jochen Hampe和同事對德國兩組人群進(jìn)行了大范圍的基因相關(guān)性研究,，同時還跟蹤德國和智利患此疾病的人群。他們發(fā)現(xiàn),，單個的基因變異能夠改變肝臟的一種膽固醇運輸者ABCG8序列,，從而認(rèn)為這種基因的變異與膽結(jié)石病有關(guān)。
膽汁是由肝臟產(chǎn)生的,，并儲存在膽囊中,，當(dāng)身體需要消化脂肪時，它就會從膽囊中釋放出來,。而當(dāng)膽固醇或膽紅素等膽汁成分水平升高并變成石頭時,，膽結(jié)石就發(fā)生了，因此,，切除膽囊是目前治療膽結(jié)石最常用的方法,。新研究認(rèn)為ABCG8的變異促進(jìn)更多的膽固醇轉(zhuǎn)化為膽汁。（援引科學(xué)時報）
原始出處:
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: [email protected]
