Cholesterol Gallstones : Genetics

Comments:
Genetics of Cholesterol Gallstones: First degree relatives of patients with gallstones have 2-to-4 fold higher risk of developing gallstones. A genetic predisposition is present in Pima Indians and certain North and South American Indian tribes. Several classes of genes, collectively referred to as LITH genes, have been identified. They encode proteins located both in the liver as well as the intestine. Polymorphisms as well as mutations in these genes lead to supersaturation of bile with cholesterol and confer high risk of cholesterol gallstones.

LITH Genes: 1) membrane lipid transporters (ABCG5/G8, ABCB4, SLC10A2 (IBAT), SLCO1B1); 2) lipid regulatory enzymes (CYP7A1, UGT1A1); 3) intracellular lipid regulatory transporters (CETP); 4) lipid regulatory transcription factors (NR1H4); 5) lipoprotein receptors (APOA1, APOB, APOC1, LRPAP1); 6) hormone receptors in the gallbladder (CCK1R, ESR2, AR, ADRB3) and 7) biliary mucins.

The image shows localization of polymorphisms and missense mutations on a model of ABCG5/G8 heterodimer crystal structure. Image source: Patel SB, Graf GA, and Temel RE. ABCG5 and ABCG8 : more than a defense against xenosterols. J. Lipid Res. 2018. 59:1103-1113. Used under CC BY Attribution 4.0 International.