Pathogenesis of gallstone formation: updated inventory of human lithogenic genes

Lammert, Frank; Sauerbruch, Tilman

doi:10.1007/978-1-4020-8833-9_9

Cited by 1 publication

(2 citation statements)

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“…Some of the genes can be termed causative, leading directly by bile lipid dysfunction (e.g., a gain in function of ABCG5/G8), whereas others (e.g., apolipoprotein B and apolipoprotein C1) represent genetic modifiers that exhibit a lithogenic effect only in the setting of a primary genetic risk factor. Where established, Table 1 also lists gene variants and potential pathophysiological mechanism involved (36).…”

Section: Genetic Analysis Of Cholesterol Gallstone Formationmentioning

confidence: 99%

“…Interestingly this common susceptibility gene (Table 1) was predicted by QTL mapping in inbred mice (43). By contrast, polymorphisms in the apolipoprotein (APO) AI, B, and C1 genes and the cholesterol ester transfer protein are modifiers, but a cholelithogenic role for APOE polymorphisms has been discounted (36).…”

Section: Genetic Analysis Of Cholesterol Gallstone Formationmentioning

confidence: 99%

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Biliary lipids and cholesterol gallstone disease

Wang

Cohen

Carey

2009

Journal of Lipid Research

173

144

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Biliary lipids are a family of four dissimilar molecular species consisting of a mixture of bile salts (substituted cholanoic acids), phospholipids, mostly (.96%) diacylphosphatidylcholines, unesterified cholesterol, and bilirubin conjugates known trivially as lipopigments. The primary pathophysiological defect in cholesterol gallstone disease is hypersecretion of hepatic cholesterol into bile with less frequent hyposecretion of bile salts and/or phospholipids. Several other gallbladder abnormalities contribute and include hypomotility, immune-mediated inflammation, hypersecretion of gelling mucins, and accelerated phase transitions; there is also reduced intestinal motility that augments "secondary" bile salt synthesis by the anaerobic microflora. Cholesterol nucleation is initiated when unilamellar vesicles of cholesterol plus biliary phospholipids fuse to form multilamellar vesicles. From these "plate-like" cholesterol monohydrate crystals, the building blocks of macroscopic stones are nucleated heterogeneously by mucin gel. Multiple Lith gene loci have been identified in inbred mice, paving the way for discovery of an ever-increasing number of LITH genes in humans. Because of the frequency of the metabolic syndrome today, insulin resistance and LITH genes all interact with a number of environmental cholelithogenic factors to cause the gallstone phenotype. This review summarizes current concepts of the physical-chemical state of biliary lipids in health and in lithogenic bile and outlines the molecular, genetic, hepatic, and cholecystic factors that underlie the pathogenesis of cholesterol gallstones.-Wang, D. Q-H., D. E. Cohen, and M. C. Carey. Biliary lipids and cholesterol gallstone disease. J. Lipid Res. 2009. 50: S406-S411.

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Section: Genetic Analysis Of Cholesterol Gallstone Formationmentioning

confidence: 99%

Section: Genetic Analysis Of Cholesterol Gallstone Formationmentioning

confidence: 99%