Analysis of the ileal bile acid transporter gene, SLC10A2, in subjects with familial hypertriglyceridemia
Analysis of the ileal bile acid transporter gene, SLC10A2, in subjects with familial hypertriglyceridemia
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DOI：
10.1161/hq1201.100262
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发表时间：
2001-12-01
影响因子：
8.7
通讯作者：
Dawson, PA
中科院分区：
文献类型：
--
作者：
Love, MW;Craddock, AL;Dawson, PA
家族性高脂血症（FHTG），一种以血浆极低密度脂蛋白甘油三酯水平升高为特征的疾病。与胆汁酸的肠吸收受损有关。本研究的目的是检验这一假设，即胆汁酸的主动回肠吸收缺陷是FHTG的主要原因。采用单链构象多态性分析方法检测回肠Na+/胆汁酸协同转运蛋白基因（SLC 10A 2）的FHTG相关突变。对20例胆汁酸代谢异常的高胆固醇血症患者进行分析，发现SLC 10A 2基因5'侧翼序列有3个错义突变（V98 I、V159 I和A171 S），1个密码子216的移码突变（646 insG）和4个多态性。SLC 10A 2错义突变和5'侧翼序列多态性与高胆固醇血症患者的胆汁酸产生或转换无关，并且在未受影响的对照受试者中同样普遍。在转染的COS细胞中，V981、V1591和A171 S亚型都与野生型SLC 10A 2类似地转运胆汁酸。646 insG移码突变废除了转染COS细胞中的胆汁酸转运活性，但仅在单个FHTG患者中发现。这些发现表明FHTG患者肠道胆汁酸吸收减少通常与SLC 10A 2的遗传缺陷无关。
Familial hypertriglyceridemia (FHTG), a disease characterized by elevated plasma very low density lipoprotein triglyceride levels. has been associated with impaired intestinal absorption of bile acids. The aim of this study was to test the hypothesis that defects in the active ileal absorption of bile acids are a primary cause of FHTG. Single-stranded conformation polymorphism analysis was used to screen the ileal Na+/bile acid cotransporter gene (SLC10A2) for FHTG-associated mutations. Analysis of 20 hypertriglyceridemic patients with abnormal bile acid metabolism revealed 3 missense mutations (V98I, V159I, and A171S), a frame-shift mutation (646insG) at codon 216, and 4 polymorphisms in the 5' flanking sequence of SLC10A2. The SLC10A2 missense mutations and 5' flanking sequence polymorphisms were not correlated with bile acid production or turnover in the hypertriglyceridemic patients and were equally prevalent in the unaffected control subjects. In transfected COS cells, the V981, V1591, and A171S isoforms all transported bile acids similar to the wild-type SLC10A2. The 646insG frame-shift mutation abolished bile acid transport activity in transfected COS cells but was found in only a single FHTG patient. These findings indicate that the decreased intestinal bile acid absorption in FHTG patients is not commonly associated with inherited defects in SLC10A2.