Investigation of the Lith1 candidate genes ABCB11 and LXRA in human gallstone disease

Research output: Contribution to journalResearch articleContributedpeer-review


  • Clemens Schafmayer - , Kiel University (Author)
  • Jürgen Tepel - , Kiel University (Author)
  • Andre Franke - , Kiel University (Author)
  • Stephan Buch - , Kiel University (Author)
  • Sören Lieb - , Kiel University (Author)
  • Marcus Seeger - , Kiel University (Author)
  • Frank Lammert - , University of Bonn (Author)
  • Bernd Kremer - , Kiel University (Author)
  • Ulrich R. Fölsch - , Kiel University (Author)
  • Fred Fändrich - , Kiel University (Author)
  • Stefan Schreiber - , Kiel University, POPGEN (Author)
  • Jochen Hampe - , Kiel University (Author)


Genetic susceptibility in the causation of gallbladder diseases was recognized as early as 1937. A major gallstone susceptibility locus (Lith1) was identified in 1995 by quantitative trait locus mapping in mice. Two attractive positional and functional candidate genes in LXRA and ABCB11 are located in this interval. ABCB11 is associated with progressive familial cholestasis. This study was undertaken to investigate LXRA and ABCB11 as candidate genes for gallstone disease in humans. Eight hundred and ten patients who underwent cholecystectomy for symptomatic gallstone disease (median age of onset, 50 years) were compared with 718 sex-matched control individuals. Control individuals were sonographically free of gallstones. Haplotype tagging and all known coding single nucleotide polymorphisms (SNPs) were genotyped for ABCB11 (n = 29) and LXRA (n = 10). The investigated high-risk patient sample provides a power of greater than 80% for the detection of odds ratios down to 1.55. No evidence of association of the two genes in the single point tagging markers, coding variants or in the sliding window haplotype analysis was detected (all nominal single-point P values ≥ .08). In conclusion, in the investigated German sample, no evidence of association of ABCB11 and LXRA to gallstone susceptibility was detected. The gallstone trait is not allelic to progressive familial cholestasis at the ABCB11 locus. Systematic fine mapping of the Lith1 region is required to identify the causative genetic variants for gallstone in mice and humans.


Original languageEnglish
Pages (from-to)650-657
Number of pages8
Issue number3
Publication statusPublished - Sept 2006
Externally publishedYes

External IDs

PubMed 16941683
ORCID /0000-0003-2928-015X/work/146166319


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