title: Dissecting the genetic heterogeneity of gallbladder stone formation.
abstract: Gallstone disease affects almost 20% of individuals in Westernized countries. As its incidence in the developing countries is rising considerably, currently, it is the second most common gastroenterological condition worldwide. Gallstone formation is driven by an interaction between genetic and environmental risk factors. Previous studies have demonstrated that the genetic background accounts for ~25% of the total disease risk. Linkage and case-control studies of candidate genes and recent genome-wide studies have identified multiple lithogenic genes, in particular the hepatocanalicular cholesterol transporter ABCG5/G8 and the bilirubin conjugating enzyme UGT1A1, as major genetic determinants of gallstones in humans. In this review, we summarize the recent findings related to the genetics of cholelithiasis, update the "inventory" of human lithogenic genes, and relate the genetic studies to the pathobiologic background of the disease. In closing, future applications of genetic testing for gallstone carriers and asymptomatic family members are addressed.
authors.affiliation: Department of Medicine II, Saarland University Hospital, Homburg, Germany.
authors.forename: Marcin
authors.initials: M
authors.lastname: Krawczyk
authors.forename: David Q-H
authors.initials: DQ
authors.lastname: Wang
authors.forename: Piero
authors.initials: P
authors.lastname: Portincasa
authors.forename: Frank
authors.initials: F
authors.lastname: Lammert
mesh_terms: D000071018:ATP Binding Cassette Transporter, Subfamily G, Member 5; D000071019:ATP Binding Cassette Transporter, Subfamily G, Member 8; D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D000818:Animals; D042882:Gallstones / Q000235:genetics* / Q000628:therapy; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D014453:Glucuronosyltransferase / Q000235:genetics; D040941:Heredity; D006801:Humans; D008074:Lipoproteins / Q000235:genetics; D010641:Phenotype; D011110:Polymorphism, Genetic; D018570:Risk Assessment; D012307:Risk Factors; D000099148:UGT1A1 Enzyme
chemical_list: D000071018:ATP Binding Cassette Transporter, Subfamily G, Member 5; D000071019:ATP Binding Cassette Transporter, Subfamily G, Member 8; D018528:ATP-Binding Cassette Transporters; D014453:Glucuronosyltransferase; D008074:Lipoproteins; D000099148:UGT1A1 Enzyme; C416945:ABCG5 protein, human; C416946:ABCG8 protein, human