Z Gastroenterol 2013; 51 - V_2_02
DOI: 10.1055/s-0032-1331962

Gallstone disease is linked to the Gilbert-Meulengracht UGT1A1*28 variant: case-control analysis of Swedish twins

M Krawczyk 1, HU Marschall 2, F Grünhage 1, D Katsika 2, C Einarsson 2, F Lammert 1
  • 1Saarland University Medical Center, Department of Medicine II, Homburg, Germany
  • 2Sahlgrenska Academy, University of Gothenburg, Institute of Medicine, Department of Internal Medicine, Gothenburg, Sweden

Background and Aims: The Gilbert-Meulengracht syndrome-associated functional TATA box variant UGT1A1*28 (A(TA)7TAA) increases susceptibility to pigment gallstone formation in the setting of haemolytic anemias [1]. Latest studies demonstrated that carriers of this variant bear an increased risk of cholesterol stones as well [2]. Here we investigate the UGT1A1 variant as a determinant of gallstone disease in a unique cohort of Swedish Twins.

Patients and Methods: The Swedish Twin Registry was merged with the Hospital Discharge and Causes of Death Registries for gallstone disease-related diagnoses and screened for monozygotic (MZ) twins with GD living in the Stockholm area. Screening of the TwinGene database for gallstone disease resulted in additional concordant twins. In total, we included 109 concordantly stone-free MZ and 126 stone-free independent DZ twins as controls. UGT1A1*28 genotyping was performed using PCR-based assays with 5'-nuclease and fluorescence detection (TaqMan).

Results: Overall, we achieved 100% genotyping success and detected an overrepresentation of heterozygotes in cases as compared to controls (55% vs. 43%). The case-control association tests showed a significantly (P<0.05) increased risk of developing gallstones (OR=1.62, 95% CI 1.00–2.63) in [GT] heterozygotes as compared to homozygous carriers of the common [G] allele. Moreover, we detected a trend (P=0.075) for enhanced gallstone risk in combined analysis of the [GT] and [TT] individuals as compared to individuals carrying the common [GG] variant (OR=1.52, 95% CI 0.97–2.44).

Conclusion: These results from Swedish twins not suffering from haemolytic anemia confirm the Gilbert-Meulengracht syndrome variant as a major genetic determinant of gallstone disease. Our observation underscores the notion that increased bilirubin levels in bile may initiate formation of cholesterol stones.

[1] Vasavda et al. Br J Haematol 2007.

[2] Buch et al. Gastroenterology 2010.