Bile acid synthesis is increased in Chilean Hispanics with gallstones and in gallstone high-risk Mapuche Indians.
OBJECTIVE
Gallstone disease is an important, costly health-care problem in Western societies. It is still unclear whether hepatic lipid regulatory enzymes play primary or secondary roles in gallstone formation. In this study, the aim was to investigate whether the synthesis of bile acids and cholesterol is increased in gallstone disease and to test whether such a metabolic change, if present, might occur before gallstone formation.


METHODS
A total of 125 Chilean Hispanic women (80 without gallstones and 45 with gallstones) matched for age and body mass index were investigated, along with 40 Chilean Mapuche Indian women (20 without gallstones and 20 with gallstones), a population group in which the prevalence for gallstone disease is very high. Fasting blood plasma samples were assayed for 7 alpha-hydroxy-4-cholesten-3-one and lathosterol, 2 strong indicators for hepatic bile acid and body cholesterol synthesis, respectively.


RESULTS
Plasma 7 alpha-hydroxy-4-cholesten-3-one levels, corrected for plasma cholesterol, were significantly increased by 50% in Hispanic women with gallstones as compared with gallstone-free Hispanics (P < 0.006). As compared with Hispanic women without gallstones, plasma 7 alpha-hydroxy-4-cholesten-3-one levels were increased by > or =100% (P < 0.002) in Mapuche Indian women, independently of whether gallstones were present. Plasma lathosterol, corrected for plasma cholesterol, was significantly increased by 22% in Hispanic women with gallstones and in Mapuche Indian women compared with Hispanic women.


CONCLUSIONS
The results indicate that the synthesis of bile acids and cholesterol is induced in gallstone disease and precedes gallstone development. These inductions presumably occur as a response to an increased intestinal loss of bile acids.
Center for Metabolim and Endocrinology, and Department of Medicine, Karolinska Institute, Huddinge University Hospital, Stockholm, Sweden.
Cecilia
C
Gälman
Juan Francisco
JF
Miquel
Rosa Maria
RM
Pérez
Curt
C
Einarsson
Lars
L
Ståhle
Guillermo
G
Marshall
Flavio
F
Nervi
Mats
M
Rudling
D000328:Adult; D001647:Bile Acids and Salts / Q000096:biosynthesis*; D016022:Case-Control Studies; D002677:Chile / Q000208:ethnology; D002783:Cholestenones / Q000097:blood; D002784:Cholesterol / Q000097:blood; D005260:Female; D042882:Gallstones / Q000097:blood / Q000209:etiology*; D006630:Hispanic or Latino; D006801:Humans; D007199:Indians, South American; D008875:Middle Aged; D012307:Risk Factors
D001647:Bile Acids and Salts; D002783:Cholestenones; C002656:7 alpha-hydroxy-4-cholesten-3-one; C001521:lathosterol; D002784:Cholesterol