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Genetic analysis of cholesterol gallstone formation: Searching for Lith (gallstone) genes

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Abstract

The genetics of cholesterol cholelithiasis is complex because a number of interacting genes regulate biliary cholesterol homeostasis. Quantitative trait locus (QTL) analysis is a powerful method for identifying primary ratelimiting genetic defects and discriminating them from secondary downstream lithogenic effects caused by mutations of the primary genes. The subsequent positional cloning of such genes responsible for QTLs may lead to the discovery of pathophysiologic functions of Lith (gallstone) genes. In this review, we present a map of candidate genes for Lith genes that may determine gallstone susceptibility in mice. The physical-chemical, pathophysiologic, and genetic studies of Lith genes in bile, liver, gallbladder, and intestine will be crucial for elucidating the genetic mechanisms of cholesterol gallstone disease in mice and in humans. Because exceptionally close homology exists between mouse and human genomes, the orthologous human LITH genes can often be recognized after mouse genes are identified.

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  1. Harvard Medical School, Liver Center, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, DA 601, 02215, Boston, MA, USA

    David Q-H. Wang MD, PhD & Nezam H. Afdhal MD

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  1. David Q-H. Wang MD, PhD
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Wang, D.QH., Afdhal, N.H. Genetic analysis of cholesterol gallstone formation: Searching for Lith (gallstone) genes. Curr Gastroenterol Rep 6, 140–150 (2004). https://doi.org/10.1007/s11894-004-0042-1

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