Absence of dysfunctional ileal sodium-bile acid cotransporter gene mutations in patients with adult-onset idiopathic bile acid malabsorption
Absence of dysfunctional ileal sodium-bile acid cotransporter gene mutations in patients with adult-onset idiopathic bile acid malabsorption
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DOI：
10.1080/003655201750422693
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发表时间：
2001-10-01
影响因子：
1.9
通讯作者：
Qvist, P
中科院分区：
文献类型：
--
作者：
Montagnani, M;Love, MW;Qvist, P
背景：先天性肠胆汁酸吸收不良（IBAM）与回肠顶端钠依赖性胆汁酸转运蛋白（ASBT）的功能障碍突变有关。本研究的目的是确定 ASBT 基因 (SLC10A2) 的突变是否易导致成人特发性胆汁酸吸收不良和慢性水样腹泻的发生。方法：从先前根据临床数据和考来烯胺反应诊断的 13 名成年 IBAM 患者中获取基因组 DNA。以及Se-75-高胆酸牛磺酸（SeHCAT）检测值异常，通过单链构象多态性分析（SSCP）和DNA测序筛选ASBT基因是否存在突变或多态性。结果：13例成年IBAM患者中有5例检测到ASBT基因多态性。 4 名患者因外显子 3 中常见的多态性而杂合，导致密码子 171 (A171S) 处丙氨酸被丝氨酸取代。另一位受试者的外显子 I 的多态性是杂合的，该多态性导致密码子 98 (V981) 处缬氨酸被异亮氨酸取代。这些功能多态性也在未受影响的受试者中发现，并且似乎不会影响 ASBT 功能。结论：成人发病的 IBAM 与 SLC10A2 基因编码区或内含子/外显子连接处的功能障碍突变没有直接关系。在没有明显的回肠疾病或肠蠕动缺陷的情况下，回肠胆汁酸转运蛋白的不适当下调或回肠胆汁酸转移到门静脉循环中的缺陷可以解释这种形式的成人IBAM。
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 Se-75-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 I 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 ilea] 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.