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Investigation of the Lith1 candidate genes ABCB11 and LXRA in human gallstone disease
Author(s) -
Schafmayer Clemens,
Tepel Jürgen,
Franke Andre,
Buch Stephan,
Lieb Sören,
Seeger Marcus,
Lammert Frank,
Kremer Bernd,
Fölsch Ulrich R.,
Fändrich Fred,
Schreiber Stefan,
Hampe Jochen
Publication year - 2006
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.21289
Subject(s) - single nucleotide polymorphism , haplotype , candidate gene , genetics , locus (genetics) , biology , odds ratio , gallstones , medicine , allele , gastroenterology , genotype , gene
Abstract 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. (H EPATOLOGY 2006;44:650–657.)