Gallstones: Environment, Lifestyle and Genes

Abstract

Gallstone disease represents one of the most common and costly gastroenterological disorders. In Germany, 0.25% of the population undergo cholecystectomy per year, and cholelithiasis incurs annual medical expenses of more than USD 6.5 billion in the United States. The paradigm of environmental risk factors for gallstones has lately been challenged by genetic studies in experimental models and humans. The analysis of more than 40,000 Swedish twin pairs with gallstones demonstrated that genetic factors account for 25% of the phenotypic variance. Since then, studies employing genome-wide association analysis, case-control cohorts and analysis of sib-pairs in families with gallstones have expanded our knowledge of ‘gallstone genes’. Indeed, gallstone disease phenotypes are likely to result from the complex interaction of genetic factors, chronic overnutrition with carbohydrates, depletion of dietary fibre and other not fully defined environmental factors including physical inactivity and infections. This hypothesis is supported by the profound increases of cholesterol gallstone prevalence rates in Native Americans, post-war European countries and current urban centres in East Asia, all of which were associated with ‘westernized’ nutrition. Herein, we summarise the spectrum of environmental and genetic risk factors which should pave the way to ‘personalised’ strategies for the prevention and therapy of gallstones.

The diameter of the common bile duct in an asymptomatic Taiwanese population: Measurement by magnetic resonance cholangiopancreatography

“…Elevated blood sugar and cholesterol levels are known to be risk factors for saturated bile and gallstone formation, 23 and although viral hepatitis in general is not directly related to biliary dilatation, in rare circumstances it can result in cholestasis and biliary dilatation. 24 Hepatitis B and C are also endemic in Taiwan with a high prevalence rate.…”

Claudin-related intestinal diseases

“…Of these, approximately 25% become clinically apparent and usually result in surgical removal of the gallbladder. Gallstones develop because of an imbalance in bile composition [5,6]. Bile composition relies, among other things, on the content of water but the exact molecular mechanisms how water flow is regulated and how it contributes to bile flow in the hepatobiliary system is still unresolved.…”

Antilithiasic and Hypolipidaemic Effects ofRaphanus sativusL.var. nigeron Mice Fed with a Lithogenic Diet

“…This disease is strongly associated with atherosclerosis and metabolic syndrome [3], and its pharmacological treatment is limited, being cholecystectomy, an invasive surgical treatment, the only treatment for symptomatic gallstones [4]. Cholesterol gallstones formation is a complex process mediated by genetic and environmental factors [5, 6]. Many proteins (ATP-binding cassette (ABC)) are implicated in its formation, mainly the biliary lipids transporters ABCB4, ABCB11, ABCG5, ABCG8, ABCC7, and Niemann-Pick C1L1 protein, and these transporters are regulated in the liver by several transcription factors, including nuclear receptors farnesoid X receptor and liver X receptors [7–9].…”