SPECIAL REPORTS AND REVIEWS Cholesterol Gallstone Susceptibility Loci: A Mouse Map, Candidate Gene Evaluation, and Guide to Human LITH Genes

摘要: Cholesterol gallstones are prevalent and costly, chiefly among developed countries. In addition to numerous environmental risk factors, a complex genetic basis determines the for developing cholesterol gallstones. Rather than monogenic mutations that rare occur in limited populations, predisposition gallstone susceptibility general populations arises from polymorphisms multiple genes, each making small contribution overall risk. Because mouse human genomes conserved only critical subset of homologous genes appears rate limiting these species, map lithogenic (Lith) loci provides “roadmap” discovery LITH genes. Quantitative trait locus (QTL) mapping was employed identify Lith mice. Repeated detection colocalizing QTLs 9 crosses 12 genetically diverse progenitor strains suggests identification most major QTLs, including Lith1‐Lith23. Therefore, using this knowledge, our priority is predict To date, predominantly, prior knowledge gene-product function invoked postulate causal roles susceptibility. Unfortunately, few such colocalized with empirical loci, suggesting absence causality or very contributions. Consequently, we present systematic comprehensive analysis literature support refute contributions by located within regions QTLs. We envisage based on translational approach will provide targets development new means prevention nonsurgical management cholelithiasis.