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Volume 2013 (2013), Article ID 298421, 10 pages
Review Article

Current Views on Genetics and Epigenetics of Cholesterol Gallstone Disease

1Division of Internal Medicine Hospital of Bisceglie, 76011 Bisceglie, Italy
2Saint Louis University School of Medicine, Division of Gastroenterology and Hepatology, Department of Internal Medicine, Edward Doisy Research Center, St. Louis, MO 63104, USA
3Clinica Medica “A. Murri”, Department of Biomedical Sciences & Human Oncology, University “Aldo Moro“ of Bari Medical School, 70124 Bari, Italy
4European Society for Clinical Investigation (ESCI), 3584 CJ Utrecht, The Netherlands

Received 28 January 2013; Revised 6 March 2013; Accepted 20 March 2013

Academic Editor: Gloria L. Vega

Copyright © 2013 Agostino Di Ciaula et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Cholesterol gallstone disease, one of the commonest digestive diseases in western countries, is induced by an imbalance in cholesterol metabolism, which involves intestinal absorption, hepatic biosynthesis, and biliary output of cholesterol, and its conversion to bile acids. Several components of the metabolic syndrome (e.g., obesity, type 2 diabetes, dyslipidemia, and hyperinsulinemia) are also well-known risk factors for gallstones, suggesting the existence of interplay between common pathophysiological pathways influenced by insulin resistance, genetic, epigenetic, and environmental factors. Cholesterol gallstones may be enhanced, at least in part, by the abnormal expression of a set of the genes that affect cholesterol homeostasis and lead to insulin resistance. Additionally, epigenetic mechanisms (mainly DNA methylation, histone acetylation/deacetylation, and noncoding microRNAs) may modify gene expression in the absence of an altered DNA sequence, in response to different lithogenic environmental stimuli, such as diet, lifestyle, pollutants, also occurring in utero before birth. In this review, we will comment on various steps of the pathogenesis of cholesterol gallstones and interaction between environmental and genetic factors. The epigenomic approach may offer new options for therapy of gallstones and better possibilities for primary prevention in subjects at risk.