Absence of Dysfunctional Ileal Sodium?Bile Acid Cotransporter Gene Mutations in Patients with Adult-Onset Idiopathic Bile Acid Malabsorption

• Published in: Scandinavian journal of gastroenterology 2001, Vol.36 (10), p.1077-1080
• Main Authors: MONTAGNANI, M, LOVE, M. W, RÖSSEL, P, DAWSON, P. A, QVIST, P
• Format: Article
• Language: English
• Subjects: Adult; Bile Acid Diarrhea Gene Mutation Gene Polymorphism Malabsorption; Bile Acids and Salts - metabolism; Biological and medical sciences; Carrier Proteins - genetics; Diarrhea - genetics; Down-Regulation - physiology; Female; Gastroenterology. Liver. Pancreas. Abdomen; Humans; Malabsorption Syndromes - genetics; Male; Medical sciences; Mutation - genetics; Organic Anion Transporters, Sodium-Dependent; Other diseases. Semiology; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Symporters
• ISSN: 0036-5521; 1502-7708
• DOI: 10.1080/003655201750422693

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 (V98I). 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.