title: [Molecular genetics of cholesterol cholelithiasis: identification of human and murine gallstone genes].
abstract: Cholesterol cholelithiasis is one of the most common gastroenterological diseases in Western countries. It is a polygenic disease resulting from disturbed biliary cholesterol homeostasis. Association studies identified six human gallstone candidate genes. Polymorphisms in the genes encoding the apolipoproteins B and E, phospholipid flippase ( ABCB4), cholesterol ester transfer protein ( CETP), cholesterol-7alpha-hydroxylase ( CYP7A1) and ileal bile acid transporter ( SLC10A2) are correlated with gallstone prevalence. Quantitative Trait Locus (QTL) analysis localises additional unknown gallstone genes in inbred mice. Based on the natural variation of cholesterol gallstone susceptibility among different inbred strains, 5 lithogenic ( Lith) loci have been identified. Hepatobiliary transporters (e. g. bile salt export pump Abcb11) and key proteins of the lipoprotein metabolism (e. g. hepatic lipase Lipc) could be established as creedal candidate genes for Lith loci. The rapid progress of mouse and human genome projects provides the basis for the analysis of orthologous human LITH genes in gallstone patients, which might offer new prospects for individual risk assessment and molecular targets for stone prevention.
authors.affiliation: Medizinische Klinik III, Universitätsklinikum der RWTH Aachen, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Figge
authors.forename: S
authors.initials: S
authors.lastname: Matern
authors.forename: F
authors.initials: F
authors.lastname: Lammert
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000235:genetics; D002769:Cholelithiasis / Q000235:genetics*; D002784:Cholesterol; D053480:Cholesterol Ester Transfer Proteins; D002874:Chromosome Mapping; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics; D014644:Genetic Variation; D005828:Genetics, Population; D006023:Glycoproteins; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics; D051379:Mice; D008815:Mice, Inbred Strains; D020412:Multifactorial Inheritance / Q000235:genetics; D029363:Organic Anion Transporters, Sodium-Dependent; D049294:Phospholipid Transfer Proteins; D010940:Plant Proteins; D011110:Polymorphism, Genetic / Q000235:genetics; D019655:Quantitative Trait, Heritable; D027981:Symporters
chemical_list: C506642:CETP protein, human; D002352:Carrier Proteins; D053480:Cholesterol Ester Transfer Proteins; D006023:Glycoproteins; D008565:Membrane Proteins; D029363:Organic Anion Transporters, Sodium-Dependent; D049294:Phospholipid Transfer Proteins; D010940:Plant Proteins; D027981:Symporters; C071908:sodium-bile acid cotransporter; D003577:Cytochrome P-450 Enzyme System; D002784:Cholesterol
vernacular_title: Molekulargenetik der Cholesterin-Cholelithiasis: Identifizierung humaner und muriner Gallensteingene.