The potential influence of genetic variants in genes along bile acid and bile metabolic pathway on blood cholesterol levels in the population.
The liver is currently known to be the major organ to eliminate excess cholesterol from our body. It accomplishes this function in two ways: conversion of cholesterol molecules into bile acids (BAs) and secretion of unesterified cholesterol molecules into bile. BAs are synthesized in the hepatocytes, secreted into bile and delivered to the lumen of the small intestine where they act as detergents to facilitate absorption of fats and fat-soluble vitamins. About 95% of BAs are recovered in the ileum during each cycle of the enterohepatic circulation. Five percent are lost and replaced by newly synthesized BAs, which amounts to approximately 500 mg/day in adult humans. In contrast to the efficiency of the BAs' enterohepatic circulation, 50% of the 1000 mg of cholesterol secreted daily into bile is lost in feces. It is known that rare human mutations in certain genes in bile acid and bile metabolic pathway influence blood cholesterol levels. With the recent success of genome-wide association studies, we are convinced that common genetic variants also play a role in the genetic architecture of plasma lipid traits. In this review, we summarized the current state of knowledge about genetic variations in bile acid and bile metabolic pathway, and assessed their impact on blood cholesterol levels and cholesterol metabolic kinetics in the population.
Lu
Yingchang
Y
Division of Human Nutrition, Wageningen University and Research Center, PO Box 8129, 6700 EV Wageningen, The Netherlands. kevin.lu@wur.nl
Feskens
Edith J M
EJ
Boer
Jolanda M A
JM
Müller
Michael
M
D000071018:ATP Binding Cassette Transporter, Subfamily G, Member 5; D000071019:ATP Binding Cassette Transporter, Subfamily G, Member 8; D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D001647:Bile Acids and Salts / Q000096:biosynthesis; D002784:Cholesterol / Q000097:blood / Q000378:metabolism*; D002790:Cholesterol 7-alpha-Hydroxylase / Q000235:genetics; D004764:Enterohepatic Circulation / Q000502:physiology; D014644:Genetic Variation; D051557:Hepatocyte Nuclear Factor 4 / Q000235:genetics; D008074:Lipoproteins; D000071518:Liver X Receptors; D008565:Membrane Proteins / Q000235:genetics; D026901:Membrane Transport Proteins; D057093:Orphan Nuclear Receptors / Q000235:genetics
C416945:ABCG5 protein, human; C416946:ABCG8 protein, human; D000071018:ATP Binding Cassette Transporter, Subfamily G, Member 5; D000071019:ATP Binding Cassette Transporter, Subfamily G, Member 8; D018528:ATP-Binding Cassette Transporters; D001647:Bile Acids and Salts; C496592:HNF4A protein, human; D051557:Hepatocyte Nuclear Factor 4; D008074:Lipoproteins; D000071518:Liver X Receptors; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; C410800:NPC1L1 protein, human; D057093:Orphan Nuclear Receptors; D002784:Cholesterol; D002790:Cholesterol 7-alpha-Hydroxylase