title: Investigation of the Lith6 candidate genes APOBEC1 and PPARG in human gallstone disease.
abstract: 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 gamma (PPARG) are located in this interval.
  
  
  OBJECTIVE
  To investigate APOBEC1 and PPARG as candidate genes for common symptomatic gallstone disease in humans.
  
  
  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 > or =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.
authors: Department of General Surgery and Thoracic Surgery, Christian-Albrechts-University Kiel, Kiel, Germany.
authors: Clemens
authors: C
authors: Schafmayer
authors: Henry
authors: H
authors: Völzke
authors: Stephan
authors: S
authors: Buch
authors: Jan
authors: J
authors: Egberts
authors: Annika
authors: A
authors: Spille
authors: Huberta
authors: H
authors: von Eberstein
authors: Andre
authors: A
authors: Franke
authors: Markus
authors: M
authors: Seeger
authors: Sebastian
authors: S
authors: Hinz
authors: Abdou
authors: A
authors: Elsharawy
authors: Dieter
authors: D
authors: Rosskopf
authors: Mario
authors: M
authors: Brosch
authors: Michael
authors: M
authors: Krawczak
authors: Ulrich R
authors: UR
authors: Foelsch
authors: Anton
authors: A
authors: Schafmayer
authors: Frank
authors: F
authors: Lammert
authors: Stefan
authors: S
authors: Schreiber
authors: Fred
authors: F
authors: Faendrich
authors: Jochen
authors: J
authors: Hampe
authors: Juergen
authors: J
authors: Tepel
mesh_terms: D000071479:APOBEC-1 Deaminase; D000818:Animals; D016022:Case-Control Studies; D003564:Cytidine Deaminase / Q000235:genetics*; D042882:Gallstones / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D005858:Germany; D006239:Haplotypes; D006801:Humans; D016015:Logistic Models; D051379:Mice; D016017:Odds Ratio; D047495:PPAR gamma / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci; D018570:Risk Assessment; D012307:Risk Factors
chemical_list: D047495:PPAR gamma; D000071479:APOBEC-1 Deaminase; C000605089:APOBEC1 protein, human; C000605090:Apobec1 protein, mouse; D003564:Cytidine Deaminase