The potential influence of genetic variants in genes along bile acid and bile metabolic pathway on blood cholesterol levels in the population

Lu, Yingchang; Feskens, Edith J.M.; Boer, Jolanda M.A.; Müller, Michael

doi:10.1016/j.atherosclerosis.2009.10.035

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Volume 210, Issue 1 , Pages 14-27, May 2010

The potential influence of genetic variants in genes along bile acid and bile metabolic pathway on blood cholesterol levels in the population

Yingchang Lu
- Division of Human Nutrition, Wageningen University and Research Center, PO Box 8129, 6700 EV Wageningen, The Netherlands
- National Institute for Public Health and the Environment (RIVM), PO Box 1, 3720 BA Bilthoven, The Netherlands
- Corresponding author at: Division of Human Nutrition, Wageningen University and Research Center, PO Box 8129, 6700 EV Wageningen, The Netherlands. Tel.: +31 317 485300; fax: +31 317 482782.
Edith J.M. Feskens
- Division of Human Nutrition, Wageningen University and Research Center, PO Box 8129, 6700 EV Wageningen, The Netherlands
Jolanda M.A. Boer
- National Institute for Public Health and the Environment (RIVM), PO Box 1, 3720 BA Bilthoven, The Netherlands
Michael Müller
- Division of Human Nutrition, Wageningen University and Research Center, PO Box 8129, 6700 EV Wageningen, The Netherlands
- Corresponding author. Tel.: +31 317 482590; fax: +31 317 483342.

Received 7 July 2009; received in revised form 22 October 2009; accepted 26 October 2009. published online 23 November 2009.

Abstract

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 ∼500mg/day in adult humans. In contrast to the efficiency of the BAs’ enterohepatic circulation, 50% of the 1000mg 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.