Homozygous p.Ser267Phe in SLC10A1 is associated with a new type of hypercholanemia and implications for personalized medicine
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 funct...
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Nature Portfolio
2017
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oai:doaj.org-article:2aa5ad318f384dea9833e704b8fbb7b62021-12-02T15:05:48ZHomozygous p.Ser267Phe in SLC10A1 is associated with a new type of hypercholanemia and implications for personalized medicine10.1038/s41598-017-07012-22045-2322https://doaj.org/article/2aa5ad318f384dea9833e704b8fbb7b62017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-07012-2https://doaj.org/toc/2045-2322Abstract 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.Ruihong LiuChuming ChenXuefeng XiaQijun LiaoQiong WangPaul J. NewcombeShuhua XuMinghui ChenYue DingXiaoying LiZhihong LiaoFucheng LiMinlian DuHuaiqiu HuangRuimin DongWeiping DengYe WangBinghui ZengQihao PanDanhua JiangHao ZengPak ShamYingnan CaoPatrick H. MaxwellZhi-liang GaoLiang PengYiming WangNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-8 (2017) |
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Medicine R Science Q Ruihong Liu Chuming Chen Xuefeng Xia Qijun Liao Qiong Wang Paul J. Newcombe Shuhua Xu Minghui Chen Yue Ding Xiaoying Li Zhihong Liao Fucheng Li Minlian Du Huaiqiu Huang Ruimin Dong Weiping Deng Ye Wang Binghui Zeng Qihao Pan Danhua Jiang Hao Zeng Pak Sham Yingnan Cao Patrick H. Maxwell Zhi-liang Gao Liang Peng Yiming Wang Homozygous p.Ser267Phe in SLC10A1 is associated with a new type of hypercholanemia and implications for personalized medicine |
| description |
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. |
| format |
article |
| author |
Ruihong Liu Chuming Chen Xuefeng Xia Qijun Liao Qiong Wang Paul J. Newcombe Shuhua Xu Minghui Chen Yue Ding Xiaoying Li Zhihong Liao Fucheng Li Minlian Du Huaiqiu Huang Ruimin Dong Weiping Deng Ye Wang Binghui Zeng Qihao Pan Danhua Jiang Hao Zeng Pak Sham Yingnan Cao Patrick H. Maxwell Zhi-liang Gao Liang Peng Yiming Wang |
| author_facet |
Ruihong Liu Chuming Chen Xuefeng Xia Qijun Liao Qiong Wang Paul J. Newcombe Shuhua Xu Minghui Chen Yue Ding Xiaoying Li Zhihong Liao Fucheng Li Minlian Du Huaiqiu Huang Ruimin Dong Weiping Deng Ye Wang Binghui Zeng Qihao Pan Danhua Jiang Hao Zeng Pak Sham Yingnan Cao Patrick H. Maxwell Zhi-liang Gao Liang Peng Yiming Wang |
| author_sort |
Ruihong Liu |
| title |
Homozygous p.Ser267Phe in SLC10A1 is associated with a new type of hypercholanemia and implications for personalized medicine |
| title_short |
Homozygous p.Ser267Phe in SLC10A1 is associated with a new type of hypercholanemia and implications for personalized medicine |
| title_full |
Homozygous p.Ser267Phe in SLC10A1 is associated with a new type of hypercholanemia and implications for personalized medicine |
| title_fullStr |
Homozygous p.Ser267Phe in SLC10A1 is associated with a new type of hypercholanemia and implications for personalized medicine |
| title_full_unstemmed |
Homozygous p.Ser267Phe in SLC10A1 is associated with a new type of hypercholanemia and implications for personalized medicine |
| title_sort |
homozygous p.ser267phe in slc10a1 is associated with a new type of hypercholanemia and implications for personalized medicine |
| publisher |
Nature Portfolio |
| publishDate |
2017 |
| url |
https://doaj.org/article/2aa5ad318f384dea9833e704b8fbb7b6 |
| work_keys_str_mv |
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