Analysis of ileal sodium/bile acid cotransporter and related nuclear receptor genes in a family with multiple cases of idiopathic bile acid malabsorption.
The etiology of most cases of idiopathic bile acid malabsorption (IBAM) is unknown. In this study, a Swedish family with bile acid malabsorption in three consecutive generations was screened for mutations in the ileal apical sodium-bile acid cotransporter gene (ASBT; gene symbol, SLC10A2) and in the genes for several of the nuclear receptors known to be important for ASBT expression: the farnesoid X receptor (FXR) and peroxisome proliferator activated receptor alpha (PPARalpha). The patients presented with a clinical history of idiopathic chronic watery diarrhea, which was responsive to cholestyramine treatment and consistent with IBAM. Bile acid absorption was determined using (75)Se-homocholic acid taurine (SeHCAT); bile acid synthesis was estimated by measuring the plasma levels of 7alpha-hydroxy-4-cholesten-3-one (C4). The ASBT, FXR, and PPARalpha genes in the affected and unaffected family members were analyzed using single stranded conformation polymorphism (SSCP), denaturing HPLC, and direct sequencing. No ASBT mutations were identified and the ASBT gene did not segregate with the bile acid malabsorption phenotype. Similarly, no mutations or polymorphisms were identified in the FXR or PPARalpha genes associated with the bile acid malabsorption phenotype. These studies indicate that the intestinal bile acid malabsorption in these patients cannot be attributed to defects in ASBT. In the absence of apparent ileal disease, alternative explanations such as accelerated transit through the small intestine may be responsible for the IBAM.
Montagnani
Marco
M
Dipartimento di Medicina Interna e Gastroenterologia, Università di Bologna, Bologna, Italy.
Abrahamsson
Anna
A
Gälman
Cecilia
C
Eggertsen
Gösta
G
Marschall
Hanns-Ulrich
HU
Ravaioli
Elisa
E
Einarsson
Curt
C
Dawson
Paul A
PA
D000328:Adult; D001647:Bile Acids and Salts / Q000378:metabolism*; D005192:Family Health; D005260:Female; D006801:Humans; D007082:Ileum / Q000378:metabolism; D008286:Malabsorption Syndromes / Q000235:genetics* / Q000378:metabolism; D008297:Male; D029363:Organic Anion Transporters, Sodium-Dependent / Q000235:genetics*; D010375:Pedigree; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics*; D027981:Symporters / Q000235:genetics*
D001647:Bile Acids and Salts; D029363:Organic Anion Transporters, Sodium-Dependent; D018160:Receptors, Cytoplasmic and Nuclear; D027981:Symporters; C071908:sodium-bile acid cotransporter