To the Editor:

The recently published article by von Kampen et al.[1] dissecting the pathobiology of cholesterol gall stone disease (GSD) using sophisticated genetic approaches appears to be indeed interesting in the postgenomic era. Linkage and association studies have identified the cholesterol transporter ABCG5/G8 as a genetic determinant of gallstone formation, or LITH gene, in humans.[2]

The research group reports two disease-associated variants, ABCG5-R50C and ABCG8-D19H, in pooled clinical samples (cases and controls) in human populations, including specimens from India. The study's overall quality could have been enhanced with more meaningful interpretation of the data if the authors had maintained homogeneity in case and control numbers. Stratified/subgroup analysis in females and males recruited in the study would further aid in understanding the gender-specific genetic background of cholelithiasis and gall stone formation. Further, I wish to comment that SNP T400K in the ABCG8 gene has also been investigated in GSD pathophysiology in an Indian population3; this particular genetic variant could have been included for genetic mapping in clinical samples drawn from Germany, Chile, Denmark, India, and China for a better understanding of the precise mechanism(s) of hypercholesterolemia and gallstone risk in disease-susceptible human populations. Moreover, family/twin studies and animal model studies using inbred strains of mice provide evidence that GSD is, in part, genetically determined.[4]

Therefore, a more comprehensive, well-designed global collaborative study approach is needed to fully understand the genetic basis of GSD in diverse ethnic groups and accordingly identify rational drug targets for early prevention of GSD.

  • Saumya Pandey, M.Sc., Ph.D.

  • University of Texas Medical Branch, Galveston, TX


  1. Top of page
  2. References
  • 1
    von Kampen O, Buch S, Nothnagel M, Azocar L, Molina H, Brosch M, et al. Genetic and functional identification of the likely causative variant for cholesterol gallstone disease at the ABCG5/8 lithogenic locus. Hepatology 2013 Jan 13. DOI: 10.1002/hep.26009.
  • 2
    Grünhage F, Acalovschi M, Tirziu S, Walier M, Wienker TF, Ciocan A, et al. Increased gallstone risk in humans conferred by common variant of hepatic ATP-binding cassette transporter for cholesterol. Hepatology 2007;46:793-801.
  • 3
    Siddapuram SP, Mahurkar S, Duvvuru NR, Mitnala S, Guduru VR, Rebala P, et al. Hepatic cholesterol transporter ABCG8 polymorphisms in gallstone disease in an Indian population. J Gastroenterol Hepatol 2010;25:1093-1098.
  • 4
    Lammert F, Matern S. The genetic background of cholesterol gallstone formation: an inventory of human lithogenic genes. Curr Drug Targets Immune Endocr Metabol Disord 2005;5:163-170.