Lith genes and genetic analysis of cholesterol gallstone formation

Helen H. Wang, Piero Portincasa, Nezam H. Afdhal, David Q.H. Wang

Research output: Contribution to journalReview article

28 Citations (Scopus)

Abstract

Epidemiologic investigations, clinical observations, and family and twin studies in humans, as well as gallstone prevalence investigations in inbred mouse models, support the concept that cholesterol cholelithiasis could result from a complex interaction of environmental factors and the effects of multiple undetermined genes. Quantitative trait locus (QTL) analysis is a powerful genetic method for identifying primary rate-limiting genetic defects and discriminating them from secondary downstream lithogenic effects caused by mutations of the primary genes, and the subsequent positional cloning of such genes responsible for QTLs, followed by the use of manufactured mouse strains with "knockout" or "knockin" of the genes, could lead to the discovery of lithogenic actions of gallstone (LITH) genes. The combined use of genomic strategies and phenotypic studies in inbred strains of mice has successfully resulted in the identification of many candidate LITH genes. Because there is exceptionally close homology between mouse and human genomes, the orthologous human LITH genes can be identified from the mouse study. The discovery of LITH genes and more fundamental knowledge concerning the genetic determinants and molecular mechanisms underlying the formation of cholesterol gallstones in humans will pave the way for critical diagnostic and prelithogenic preventive measures for this exceptionally prevalent digestive disease.

Original languageEnglish (US)
JournalGastroenterology Clinics of North America
Volume39
Issue number2
DOIs
StatePublished - Jun 1 2010
Externally publishedYes

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Gallstones
Cholesterol
Genes
Twin Studies
Inbred Strains Mice
Cholelithiasis
Quantitative Trait Loci
Genetic Association Studies
Human Genome
Organism Cloning
Molecular Biology
Mutation

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Lith genes and genetic analysis of cholesterol gallstone formation. / Wang, Helen H.; Portincasa, Piero; Afdhal, Nezam H.; Wang, David Q.H.

In: Gastroenterology Clinics of North America, Vol. 39, No. 2, 01.06.2010.

Research output: Contribution to journalReview article

Wang, Helen H. ; Portincasa, Piero ; Afdhal, Nezam H. ; Wang, David Q.H. / Lith genes and genetic analysis of cholesterol gallstone formation. In: Gastroenterology Clinics of North America. 2010 ; Vol. 39, No. 2.
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