title: Gallstone disease in Swedish twins: risk is associated with ABCG8 D19H genotype.
abstract: OBJECTIVE
  Recently, variants of the hepatocanalicular cholesterol hemitransporters ABCG5/8 were linked to gallstone disease; ABCG8 D19H in Caucasians and ABCG5 Q604E in Chinese. We investigated these polymorphisms in Swedish twins by merging the Swedish Twin Registry with the Hospital Discharge and Causes of Death Registries for gallstone disease-related diagnoses.
  
  
  METHODS
  All monozygotic (MZ) twins with gallstone disease alive in the Stockholm area were invited to participate. Gallstone disease was defined by entry in all above mentioned registries, questionnaire or abdominal ultrasound.
  
  
  METHODS
  ABCG5 Q604E and ABCG8 D19H genotyping was performed in 24 unique MZ and eight dizygotic (DZ) twins from concordant pairs. Screening of the TwinGene database for gallstone disease resulted in an additional 20 concordant MZ and 54 twins from concordant DZ pairs. We included 109 concordantly stone-free MZ and 126 stone-free independent DZ twins as controls.
  
  
  RESULTS
  Amongst the 341 twins, 20.8% carried at least one D19H allele as compared to 9.4% of stone-free controls. The association analysis showed that D19H positivity significantly increased the risk of gallstone disease [odds ratio (OR), 2.54; 95% confidence interval (CI), 1.33-4.82; P = 0.004]. We also found a trend for a positive association between gallstone disease and the Q604E variant (OR, 1.47; 95% CI, 1.00-2.16; P = 0.052).
  
  
  CONCLUSIONS
  Twins carrying a heterozygous or homozygous ABCG8 D19H genotype have a significantly increased risk of gallstone disease. Our study confirms the ABCG8 D19H genotype as a major risk factor for gallstone disease.
authors.affiliation: Karolinska Institutet, Department of Medicine, Division of Gastroenterology and Hepatology, Karolinska University Hospital Huddinge, Stockholm, Sweden. despina.katsika@ki.se
authors.forename: D
authors.initials: D
authors.lastname: Katsika
authors.forename: P
authors.initials: P
authors.lastname: Magnusson
authors.forename: M
authors.initials: M
authors.lastname: Krawczyk
authors.forename: F
authors.initials: F
authors.lastname: Grünhage
authors.forename: P
authors.initials: P
authors.lastname: Lichtenstein
authors.forename: C
authors.initials: C
authors.lastname: Einarsson
authors.forename: F
authors.initials: F
authors.lastname: Lammert
authors.forename: H-U
authors.initials: HU
authors.lastname: Marschall
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*; D000368:Aged; D000369:Aged, 80 and over; D004200:Diseases in Twins / Q000235:genetics*; D005260:Female; D042882:Gallstones / Q000235:genetics*; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing / Q000379:methods; D005838:Genotype; D006801:Humans; D008074:Lipoproteins / Q000235:genetics; D008297:Male; D008875:Middle Aged; D012042:Registries; D012307:Risk Factors; D014430:Twins, Monozygotic
chemical_list: C416945:ABCG5 protein, human; C416946:ABCG8 protein, human; D000071018:ATP Binding Cassette Transporter, Subfamily G, Member 5; D000071019:ATP Binding Cassette Transporter, Subfamily G, Member 8; D018528:ATP-Binding Cassette Transporters; D008074:Lipoproteins