title: Gallstone disease in Swedish twins is associated with the Gilbert variant of UGT1A1.
abstract: OBJECTIVE
  The Gilbert syndrome-associated functional TATA box variant UGT1A1*28 (A(TA)7TAA) was found to increase susceptibility to pigment gallstone formation in patients with haemolytic anaemia. Further studies in extensive cohorts demonstrated an increased risk of this variant for cholesterol gallstone disease (GD). We now investigated this polymorphism as a determinant of symptomatic GD in Swedish twins.
  
  
  METHODS
  The Swedish Twin Registry was merged with the Hospital Discharge and Causes of Death Registries and searched for GD-related diagnoses among monozygotic (MZ) twins living in the Stockholm area. In addition, we screened the TwinGene database for GD. In total, we found 44 MZ twin pairs with and eight MZ twins without GD to be evaluable. GD-free twins from TwinGene (109 concordantly MZ and 126 independent DZ) served as controls. UGT1A1*28 genotyping was performed using TaqMan assays.
  
  
  RESULTS
  Overall, 58 and 8 of 106 twins with GD were hetero- and homozygous UGT1A1 risk allele carriers respectively. The case-control association tests showed a significantly (P < 0.05) increased risk of developing GD (OR = 1.62, 95% CI 1.00-2.63) in heterozygotes carriers and in addition, a trend (P = 0.075) for an increased risk among carriers (OR = 1.52, 95% CI 0.97-2.44) of the risk allele.
  
  
  CONCLUSIONS
  These data from Swedish twins confirm the Gilbert variant as risk factor for GD. Our observation is in line with nucleation in bilirubin supersaturated bile representing an initial step in cholelithogenesis.
authors.affiliation: Sahlgrenska Academy, Institute of Medicine, Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden. hanns-ulrich.marschall@gu.se
authors.forename: Hanns-Ulrich
authors.initials: HU
authors.lastname: Marschall
authors.forename: Marcin
authors.initials: M
authors.lastname: Krawczyk
authors.forename: Frank
authors.initials: F
authors.lastname: Grünhage
authors.forename: Despina
authors.initials: D
authors.lastname: Katsika
authors.forename: Curt
authors.initials: C
authors.lastname: Einarsson
authors.forename: Frank
authors.initials: F
authors.lastname: Lammert
mesh_terms: D000071019:ATP Binding Cassette Transporter, Subfamily G, Member 8; D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D005260:Female; D042882:Gallstones / Q000000981:diagnostic imaging / Q000201:enzymology / Q000235:genetics*; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005878:Gilbert Disease / Q000201:enzymology / Q000235:genetics*; D014453:Glucuronosyltransferase / Q000235:genetics*; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012042:Registries; D012307:Risk Factors; D013548:Sweden; D014430:Twins, Monozygotic / Q000235:genetics*; D014463:Ultrasonography; D000099148:UGT1A1 Enzyme
chemical_list: D000071019:ATP Binding Cassette Transporter, Subfamily G, Member 8; D018528:ATP-Binding Cassette Transporters; D014453:Glucuronosyltransferase; D000099148:UGT1A1 Enzyme; C416946:ABCG8 protein, human