Absence of dysfunctional ileal sodium-bile acid cotransporter gene mutations in patients with adult-onset idiopathic bile acid malabsorption.
BACKGROUND
A congenital form of idiopathic intestinal bile acid malabsorption (IBAM) has been associated with dysfunctional mutations in the ileal apical sodium-dependent bile acid transporter (ASBT). The aim of this study was to determine whether mutations in the ASBT gene (SLC10A2) predispose to the development of adult-onset idiopathic bile acid malabsorption and chronic watery diarrhea.


METHODS
Genomic DNA was obtained from 13 adult IBAM patients previously diagnosed on the basis of clinical data, response to cholestyramine, and abnormal 75Se-homocholic acid taurine (SeHCAT) test values. The ASBT gene was screened for the presence of mutations or polymorphisms by single-stranded conformation polymorphism analysis (SSCP) and DNA sequencing.


RESULTS
ASBT gene polymorphisms were detected in 5 of the 13 adult IBAM patients. Four patients were heterozygous for a common polymorphism in exon 3, leading to an alanine to serine substitution at codon 171 (A171S). An additional subject was heterozygous for a polymorphism in exon 1 that causes a valine to isoleucine substitution at codon 98 (V981). These functional polymorphisms were also found in unaffected subjects and do not appear to affect ASBT function.


CONCLUSIONS
Adult-onset IBAM is not directly related to dysfunctional mutations in the coding region or intron/exon junctions of the SLC10A2 gene. In the absence of apparent ileal disease or intestinal motility defects, inappropriate down-regulation of the ileal bile acid transporter or defects in ileocyte transfer of bile acids into the portal circulation could explain this form of adult IBAM.
Montagnani
M
M
Dept. of Internal Medicine and Gastroenterology, University of Bologna, Policlinico S. Orsola, Italy.
Love
M W
MW
Rössel
P
P
Dawson
P A
PA
Qvist
P
P
D000328:Adult; D001647:Bile Acids and Salts / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics*; D003967:Diarrhea / Q000235:genetics*; D015536:Down-Regulation / Q000502:physiology; D005260:Female; D006801:Humans; D008286:Malabsorption Syndromes / Q000235:genetics*; D008297:Male; D009154:Mutation / Q000235:genetics; D029363:Organic Anion Transporters, Sodium-Dependent; D027981:Symporters
D001647:Bile Acids and Salts; D002352:Carrier Proteins; D029363:Organic Anion Transporters, Sodium-Dependent; D027981:Symporters; C071908:sodium-bile acid cotransporter