Investigation of the Lith6 candidate genes APOBEC1 and PPARG in human gallstone disease.

Clemens Schafmayer, Henry Völzke, Stephan Buch, Jan Egberts, Annika Spille, Huberta von Eberstein, Andre Franke, Markus Seeger, Sebastian Hinz, Abdou Elsharawy, Dieter Rosskopf, Mario Brosch, Michael Krawczak, Ulrich R Foelsch, Anton Schafmayer, Frank Lammert, Stefan Schreiber, Fred Faendrich, Jochen Hampe, Juergen Tepel
Year of publication:
Journal title abbreviated:
Journal title long:
Liver international
Impact factor:
The investigated high-risk patient sample provides a power of greater than 80% for the detection of odds ratios down to 1.45. No evidence of association of the two genes in the single-point tagging markers, coding variants and in the sliding window haplotype analysis was detected (all nominal single point P-values >0.04). A logistic regression analysis including age, sex and BMI as covariates was also negative (nominal P-values > or =0.08).In the investigated German samples, no evidence of association of APOBEC1 and PPARG with gallstone susceptibility was detected. Systematic fine mapping of the complete Lith6 region is required to identify the causative genetic variants for gallstone in mice and humans.Genetic susceptibility contributes to the aetiology of gallbladder diseases as shown by multiple epidemiological studies. A major gallstone susceptibility locus (Lith6) was identified in 2003 by quantitative trait locus mapping in mice. Two attractive positional and functional candidate genes in apolipoprotein B mRNA-editing protein (APOBEC1) and peroxisome proliferator-activated receptor gamma (PPARG) are located in this interval.To investigate APOBEC1 and PPARG as candidate genes for common symptomatic gallstone disease in humans.Eight hundred and ten patients who underwent cholecystectomy for symptomatic gallstone disease (median age of onset 50) were compared with 718 sex-matched control individuals. An independent additional sample included 368 gallstone patients and 368 controls. Control individuals were sonographically free of gallstones. Haplotype tagging and all known coding single nucleotide polymorphisms were genotyped for PPARG (N=32) and APOBEC1 (N=11).