Abstract

SLC10A1 codes for the sodium-taurocholate cotransporting polypeptide (NTCP), which is a hepatocellular transporter for bile acids (BAs) and the receptor for hepatitis B and D viruses. NTCP is also a target of multiple drugs. We aimed to evaluate the medical consequences of the loss of function mutation p.Ser267Phe in SLC10A1. We identified eight individuals with homozygous p.Ser267Phe mutation in SLC10A1 and followed up for 8–90 months. We compared their total serum BAs and 6 species of BAs with 170 wild-type and 107 heterozygous healthy individuals. We performed in-depth medical examinations and exome sequencing in the homozygous individuals. All homozygous individuals had persistent hypercholanemia (P = 5.8 × 10–29). Exome sequencing excluded the involvement of other BA metabolism-associated genes in the hypercholanemia. Although asymptomatic, all individuals had low vitamin D levels. Of six adults that were subjected to bone mineral density analysis, three presented with osteoporosis/osteopenia. Sex hormones and blood lipids were deviated in all subjects. Homozygosity of p.Ser267Phe in SLC10A1 is associated with asymptomatic hypercholanemia. Individuals with homozygous p.Ser267Phe in SLC10A1 are prone to vitamin D deficiency, deviated sex hormones and blood lipids. Surveillance of these parameters may also be needed in patients treated with drugs targeting NTCP.

Details

Title
Homozygous p.Ser267Phe in SLC10A1 is associated with a new type of hypercholanemia and implications for personalized medicine
Author
Liu, Ruihong 1 ; Chen, Chuming 2 ; Xia, Xuefeng 3 ; Liao, Qijun 4 ; Wang, Qiong 5 ; Newcombe, Paul J 6 ; Xu, Shuhua 7   VIAFID ORCID Logo  ; Chen, Minghui 5 ; Ding, Yue 8 ; Li, Xiaoying 9 ; Liao, Zhihong 10 ; Li, Fucheng 11 ; Du, Minlian 12 ; Huang, Huaiqiu 13 ; Dong, Ruimin 14 ; Deng, Weiping 15 ; Wang, Ye 16 ; Zeng, Binghui 17 ; Pan, Qihao 18 ; Jiang, Danhua 19 ; Zeng, Hao 19 ; Pak Sham 20 ; Cao, Yingnan 21 ; Maxwell, Patrick H 22 ; Zhi-liang Gao 2 ; Liang, Peng 2 ; Wang, Yiming 23 

1  Fifth Affiliated Hospital, Sun Yat-sen University-BGI Laboratory, Department of Experimental Medicine, The Fifth Affiliated Hospital,Sun Yat-sen University, Zhuhai, China 
2  Department of Infectious Diseases, Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; Guangdong Key Laboratory of Liver Diseases, Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China 
3  Methodist Hospital Research Institute, Weill Cornell School of Medicine, Houston, TX, USA 
4  BGI Genomics, BGI-Shenzhen, Shenzhen, China 
5  Center for Reproductive Medicine, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China 
6  MRC Biostatistics Unit, Cambridge, United Kingdom 
7  Chinese Academy of Sciences Key Laboratory of Computational Biology, Max Planck Independent Research Group on Population Genomics, CAS-MPG Partner Institute for Computational Biology, Shanghai Institute for Biological Sciences, CAS, Shanghai, China 
8  Department of Orthopaedic Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China 
9  Department of Endocrinology, Fudan Institute of Metabolic Disease, Zhongshan Hospital, Fudan University, Shanghai, China 
10  Department of Endocrinology, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China 
11  Department of Prenatal Diagnostic Center, Guangzhou Women and Children’s Medical Centre, Guangzhou Medical University, Guangzhou, China 
12  Department of Pediatrics, First Af f iliated Hospital, Sun Yat-sen University, Guangzhou, China 
13  Department of Dermatology and Venereology, Third Af f iliated Hospital, Sun Yat-sen University, Guangzhou, China 
14  Department of Cardiology, Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China 
15  Department of Dermatology, Guangdong Academy of Medical Sciences, Guangdong General Hospital, Guangzhou, China 
16  Center for Fetal Medicine, Department of Obstetrics and Gynecology, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China 
17  Guanghua School of Stomatology, Hospital of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, China 
18  Center for Prenatal Diagnosis, Sixth Affiliated Hospital, Guangzhou Medical University, Qingyuan, China 
19  Department of Medical Genetics, Center for Genome Research, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China 
20  Centre for Genomic Sciences, The University of Hong Kong, Pokfulam, Hong Kong; Department of Psychiatry, The University of Hong Kong, Pokfulam, Hong Kong; State Key Laboratory for Cognitive and Brain Sciences, The University of Hong Kong, Pokfulam, Hong Kong; Centre for Reproduction, Development and Growth, The University of Hong Kong, Pokfulam, Hong Kong 
21  Department of Pharmacology, Xinhua College, Sun Yat-sen University, Guangzhou, China 
22  School of Clinical Medicine, University of Cambridge, Cambridge, United Kingdom 
23  Fifth Affiliated Hospital, Sun Yat-sen University-BGI Laboratory, Department of Experimental Medicine, The Fifth Affiliated Hospital,Sun Yat-sen University, Zhuhai, China; Department of Medical Genetics, Center for Genome Research, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China; Department of Pharmacology, Xinhua College, Sun Yat-sen University, Guangzhou, China 
Pages
1-8
Publication year
2017
Publication date
Aug 2017
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41598-017-07012-2
ProQuest document ID
1957861458
Copyright
© 2017. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.