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Mechanisms of Disease: the genetic epidemiology of gallbladder stones

Nature Clinical Practice Gastroenterology & Hepatology volume 2, pages 423–433 (2005)Cite this article

Abstract

Cholelithiasis is one of the most prevalent and most expensive gastroenterologic diseases. It belongs to the group of complex metabolic disorders that affect humans, and its critical pathogenic mechanisms are not well defined. As a result, primary or secondary prevention strategies are sparse, and the only effective treatment is cholecystectomy. Here we provide an update on the molecular pathogenesis of gallbladder stones, evidence supporting the hypothesis that genetic factors are key elements predisposing to gallstones, and progress in human genetic studies of cholesterol stones. Data from recent identical twin, family and linkage studies provide conclusive evidence for a strong genetic component to gallstone disease. Furthermore, epidemiologic studies in at-risk populations indicate that gallstone formation is caused by multiple environmental influences and common genetic factors and their interactions. By contrast, monogenic subtypes of cholelithiasis, such as ATP-binding-cassette transporter deficiencies, appear to be rare. The summary of human association studies illustrates that distinct common gene variants might contribute to gallstone formation in different ethnic groups. The characterization of lithogenic genes in knockout and transgenic mice and the identification of many gallstone-susceptibility loci in inbred mice provide the basis for studies of the corresponding genes in patients with gallstones. The transfer of findings from mouse genetics to the bedside might lead to new strategies for individual risk assessment and reveal novel molecular targets for prevention and medical therapies.

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Figure 1: Pie diagram depicting the contribution of genetic, shared and individual environmental factors to the pathogenesis of symptomatic gallstone disease in twins.

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Acknowledgements

The authors' experimental work relating to the genetic epidemiology of gallstones was supported in part by research grants from the Deutsche Forschungsgemeinschaft and a grant from the Ministry of Science and Research of North-Rhine-Westphalia.

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Authors and Affiliations

  1. Professor of Medicine and Gastroenterology Department of Internal Medicine I, University Hospital Bonn, University of Bonn, Bonn, Germany

    Frank Lammert

  2. Head of the Department of Internal Medicine I, University Hospital Bonn, University of Bonn, Bonn, Germany

    Tilman Sauerbruch

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Correspondence to Frank Lammert.

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Lammert, F., Sauerbruch, T. Mechanisms of Disease: the genetic epidemiology of gallbladder stones. Nat Rev Gastroenterol Hepatol 2, 423–433 (2005). https://doi.org/10.1038/ncpgasthep0257

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