Biochemical and Bioinformatic Characterization of Patients with a Sodium Taurocholate Cotransporting Polypeptide Mutation

Background: SLC10A1 codes for the sodium taurocholate cotransporting polypeptide (NTCP). The SLC10A1S267F mutation is associated with loss of function of bile acid (BA) uptake and defined as a new type of hypercholanemia. This kind of hypercholanemia is characterized by high levels of serum BA. However, limited studies have been conducted on this topic. Objectives: This study aimed to describe the biochemical and bioinformatic characterization of patients with an SLC10A1S267F mutation, as well as to dissect pathogenesis in hypercholanemia. Methods: In this study, a total of 12 individuals (including 5 homozygous, 3 heterozygous, and 4 wild-type individuals) were recruited. Whole-genome sequencing (WGS) and Sanger sequencing were used to confirm the genotype. Tests of liver function, renal function, and serum lipid level, in addition to routine blood tests, were performed to evaluate the clinical consequences of patients with an SLC10A1S267F mutation. The ClinVar website and protein prediction tools were used to analyze other cholesterol and BAs related gene mutations in SLC10A1S267F patients, as well as to evaluate their possible effects on serum BA levels of patients. Results: All SLC10A1S267F homozygous patients displayed high levels of BAs. Liver and renal functions were generally normal. According to previous reports, homozygous patients are prone to vitamin D deficiency and deviated blood lipids. However, all homozygous individuals had normal levels of blood lipids, thyroid hormones, and vitamin D (25(OH)D). Moreover, except for the SLC10A1S267F mutation, according to the WGS results, multiple gene mutations were found in 5 homozygous and might affect the level of BAs, but the SLC10A1S267F mutation still is the most important reason resulting in a high level of BAs. Conclusions: This study provided a more detailed description of the SLC10A1S267F mutation-induced hypercholanemia, delivering a new idea that there might be some mutations in SLC10A1S267F homozygotes, probably influencing BA metabolism.