Genotype-phenotype landscape of Sodium taurocholate cotransporting polypeptide deficiency in Yunnan Province, China: A five-year retrospective, multi-ethnic cohort study

doi:10.4251/wjgo.123971

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World Journal of Gastrointestinal Oncology

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1948-5204

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

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Copyright: ©Author(s) 2026. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution-NonCommercial (CC BY-NC 4.0) license. No commercial re-use. See permissions. Published by Baishideng Publishing Group Inc.

World J Gastrointest Oncol. Nov 15, 2026; 18(11): 123971
Published online Nov 15, 2026. doi: 10.4251/wjgo.123971

Genotype-phenotype landscape of Sodium taurocholate cotransporting polypeptide deficiency in Yunnan Province, China: A five-year retrospective, multi-ethnic cohort study

Mei-Fen Wang, Rui Chen, Juan Li, Zhi-Kuan Cun, Qiong Li, Hong-Chao Jiang, Ji-Wei Li

Mei-Fen Wang, Rui Chen, Zhi-Kuan Cun, Qiong Li, Department of Infectious Diseases, Affiliated Children’s Hospital of Kunming Medical University (Kunming Children’s Hospital), Kunming 650228, Yunnan Province, China

Juan Li, Department of Gastroenterology, Affiliated Children’s Hospital of Kunming Medical University (Kunming Children’s Hospital), Kunming 650228, Yunnan Province, China

Hong-Chao Jiang, Clinical Research Center, Affiliated Children’s Hospital of Kunming Medical University (Kunming Children’s Hospital), Kunming 650228, Yunnan Province, China

Ji-Wei Li, Department of Pathology, Affiliated Children’s Hospital of Kunming Medical University (Kunming Children’s Hospital), Kunming 650228, Yunnan Province, China

Co-corresponding authors: Hong-Chao Jiang and Ji-Wei Li.

Author contributions: Wang MF, Chen R, Li J, Cun ZK and Li Q collected sample; Wang MF, Chen R, Jiang HC and Li JW performed the experiments; Wang MF, Jiang HC and Li JW wrote and revised the paper; all authors read and approved the final manuscript. Jiang HC and Li JW are designated as co-corresponding authors of this work. Both authors contributed equally to the conceptualization, study design, data interpretation, and manuscript revision. Jiang HC, as a Chief physician in the Department of Clinical Research Center, provided critical oversight of the clinical data collection and statistical analysis, and secured major funding support (Xingdian Talent Support Plan and Kunming Spring City Plan). Li JW, as a pathologist and clinical researcher, contributed substantially to the genetic data interpretation, variant classification according to ACMG/AMP guidelines, and drafting of the genotype-phenotype correlation analysis. The two co-corresponding authors collaborated closely throughout the research process and jointly supervised the project. Both have approved the final manuscript and agree to be accountable for all aspects of this work. Primary corresponding author: Li JW will serve as the single primary contact for all correspondence with the journal during submission, peer review, and publication processes. He takes primary responsibility for ensuring that all administrative requirements of the journal (including authorship details, ethics committee approval documentation, and conflict-of-interest forms) are properly completed.

AI contribution statement: No AI tools were used in the preparation of this manuscript. The authors assume full responsibility for the integrity, accuracy, and originality of all submitted materials.

Supported by The “Famous Doctor” Special Project of Xingdian Talent Support Plan of Yunnan Province, No. XDYC-YLWS-2023-0006; Kunming Spring City Plan High-Level Talent Training Project, Kunming Municipal Government “Spring City Famous Doctor” Special Project, No. C2020120231; Kunming Medical Science And Technology Leading Talent Project, No. 2022-SW (leader)-05; Kunming Medical University Affiliated Children’s Hospital Medical Technology Center for Pediatric Liver Disease Diagnosis and Treatment, No. 2024-SW(Tech)-04; Xingdian Talent Support Program for Medical and Health Talents Project, No. XDYC-YLWS-2023-0004; Technical Innovation Talent Training Target Project, No. 202305AD160058; Kunming Medical Science And Technology Academic Leading Talent Project, No. 2024-SW-14; and Research Project of the Yunnan Provincial Clinical Medicine Center, No. 2024YNLCYXZX0478.

Institutional review board statement: The study was conducted in accordance with the Declaration of Helsinki. The research protocol involving human data analysis was reviewed and approved by the Medical Ethics Committee of Kunming Children’s Hospital (Approval No. 20190211004) on 11 February 2019. The ethics committee granted approval for the analysis of existing data with informed consent conducted by means of notification.

Informed consent statement: All study participants, or their legal guardians, provided informed written consent prior to study enrollment.

Conflict-of-interest statement: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.

Data sharing statement: The datasets generated and/or analyzed during the current study are available from the corresponding author upon reasonable request.

Corresponding author: Ji-Wei Li, PhD, Department of Pathology, Affiliated Children’s Hospital of Kunming Medical University (Kunming Children’s Hospital), No. 288 Qianxing Street, Kunming 650228, Yunnan Province, China. km_dc_lee@163.com

Received: June 3, 2026
Revised: August 5, 2026
Accepted: September 24, 2026
Published online: November 15, 2026
Processing time: 146 Days and 21.3 Hours

Abstract

BACKGROUND

Sodium taurocholate cotransporting polypeptide deficiency (NTCPD) causes persistent hypercholanemia and neonatal cholestasis, but its genotypic and phenotypic spectrum across ethnicities and geographic backgrounds remains poorly characterized.

AIM

To characterize the genetic architecture, biochemical trajectories, and genotype-phenotype correlations of NTCPD in a multi-ethnic pediatric cohort.

METHODS

In this case cohort study, we analyzed 125 patients with genetically confirmed NTCPD from Kunming Children’s Hospital (2020-2025). Longitudinal biochemical parameters were tracked, and multivariable regression was performed to assess genotype-biochemical relationships, adjusting for age, ethnicity, and geographic location.

RESULTS

The cohort comprised 69 male and 56 female patients (83 homozygous, 25 heterozygous, and 17 compound heterozygous). The c.800C>T variant was present in all compound heterozygotes, together with 11 additional variants (four likely pathogenic variants and seven variants of uncertain significance). The cohort comprised 73 Han and 52 individuals from ethnic minority groups, predominantly Yi and Hui, distributed across 15 prefectures. Biochemical profiles indicated self-limiting hypercholanemia, with total bile acid levels declining from 178.8 ± 60.9 µmol/L (0-2 months) to 141.2 ± 77.9 µmol/L (> 4 months, P = 0.0002). Homozygous and compound heterozygous genotypes were strongly associated with hypercholanemia and vitamin E deficiency, independent of demographics. Sex-stratified analysis revealed genotype- associated elevations in aspartate aminotransferase in males and more pronounced disturbances in vitamin E and iron levels in females.

CONCLUSION

In Yunnan’s multi-ethnic population, NTCPD exhibited as self-limiting course and genetic heterogeneity across ethnic and geographic subgroups. These findings provide preliminary evidence to inform larger studies and the development of monitoring strategies.

Keywords: Sodium taurocholate cotransporting polypeptide deficiency; SLC10A1 gene; Persistent hypercholanemia; Pediatric cholestasis; Genotype-phenotype correlation

Core Tip: This 5-year retrospective study of 125 pediatric patients with sodium taurocholate cotransporting polypeptide deficiency from Yunnan Province is the largest multi-ethnic cohort to date. The results reveals that the c.800C>T founder variant predominates across 12 ethnic groups, while 11 additional variants (four likely pathogenic, seven variants of uncertain significance) contribute to allelic heterogeneity. The biochemical trajectories demonstrate self-limiting hypercholanemia with age-dependent resolution, while sex-stratified analyses uncover genotype-linked elevations in aspartate aminotransferase in males and disturbances in vitamin E and iron levels in females. These findings provide an exploratory framework for genotype-informed monitoring in ethnically diverse populations, though causality and generalizability require prospective validation.