Investigation of the Lith6 candidate genes APOBEC1 and PPARG in human gallstone disease
Article first published online: 13 AUG 2007
Volume 27, Issue 7, pages 910–919, September 2007
How to Cite
Schafmayer, C., Völzke, H., Buch, S., Egberts, J., Spille, A., Von Eberstein, H., Franke, A., Seeger, M., Hinz, S., ElSharawy, A., Rosskopf, D., Brosch, M., Krawczak, M., Foelsch, U. R., Schafmayer, A., Lammert, F., Schreiber, S., Faendrich, F., Hampe, J. and Tepel, J. (2007), Investigation of the Lith6 candidate genes APOBEC1 and PPARG in human gallstone disease. Liver International, 27: 910–919. doi: 10.1111/j.1478-3231.2007.01536.x
- Issue published online: 13 AUG 2007
- Article first published online: 13 AUG 2007
- Received 21 August 2006accepted 13 April 2007
- gallstone disease;
- Lith genes;
Background: 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 γ (PPARG) are located in this interval.
Aims: To investigate APOBEC1 and PPARG as candidate genes for common symptomatic gallstone disease in humans.
Patients and methods: 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).
Results: 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 ≥0.08).
Conclusions: 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.