Xu XG, Liu YQ, Lan ML, Liu F, Xia HM, Zeng JX. Neurotrophin-3 rs1805149A>G variant in Hirschsprung disease: An investigative study. World J Gastrointest Surg 2026; 18(2): 114724 [DOI: 10.4240/wjgs.v18.i2.114724]
Corresponding Author of This Article
Ji-Xiao Zeng, MD, Department of Pediatric Surgery, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, National Children’s Medical Center for South Central Region, Guangdong Provincial Clinical Research Center for Child Health, No. 318 Renmin Road, Guangzhou 510623, Guangdong Province, China. zengjixiao@163.com
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Clinical Trials Study
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This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Feb 27, 2026 (publication date) through Feb 26, 2026
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Journal Information of This Article
Publication Name
World Journal of Gastrointestinal Surgery
ISSN
1948-9366
Publisher of This Article
Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA
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Xu XG, Liu YQ, Lan ML, Liu F, Xia HM, Zeng JX. Neurotrophin-3 rs1805149A>G variant in Hirschsprung disease: An investigative study. World J Gastrointest Surg 2026; 18(2): 114724 [DOI: 10.4240/wjgs.v18.i2.114724]
Xiao-Gang Xu, Yan-Qing Liu, Meng-Long Lan, Fei Liu, Hui-Min Xia, Ji-Xiao Zeng, Department of Pediatric Surgery, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, National Children’s Medical Center for South Central Region, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou 510623, Guangdong Province, China
Author contributions: Xu XG, Liu YQ and Zeng JX conceived and designed the study; Xu XG, Xia HM and Zeng JX conducted the study; Liu YQ, Lan ML and Liu F contributed to data acquisition; Liu YQ, Lan ML and Liu F analyzed the data; Liu YQ, Lan ML and FL interpreted the data; Xu XG, Xia HM and Zeng JX edited the manuscript draft; Xu XG, Xia HM and Zeng JX reviewed and edited the manuscript; all authors have read and approved the manuscript.
Supported by the Science and Technology Project of Guangzhou, No. 202206080002; National Natural Science Foundation of China, No. 82170528; and Guangzhou Science and Technology Plan of Municipal University (Institute) Joint Funding, No. SL2024A03J01490.
Institutional review board statement: The study received ethical approval by the Research Ethics Committee of Guangzhou Women and Children Medical Center (Approval No. 2017102706).
Informed consent statement: Written informed consent was obtained for participation in this study. Informed consent for this study was obtained from the parent or legal guardian of any participant under 16 years of age.
Conflict-of-interest statement: This manuscript has no potential conflict of interest to disclose.
Data sharing statement: The individual genotype data generated in this study are not publicly available due to participant privacy and ethical restrictions but can be accessed through a controlled-access repository upon reasonable request to the corresponding author. Requests will be reviewed by the Guangzhou Women and Children Medical Center Ethics Committee to ensure compliance with data protection regulations.
Corresponding author: Ji-Xiao Zeng, MD, Department of Pediatric Surgery, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, National Children’s Medical Center for South Central Region, Guangdong Provincial Clinical Research Center for Child Health, No. 318 Renmin Road, Guangzhou 510623, Guangdong Province, China. zengjixiao@163.com
Received: September 28, 2025 Revised: October 31, 2025 Accepted: December 5, 2025 Published online: February 27, 2026 Processing time: 152 Days and 23.5 Hours
Abstract
BACKGROUND
Hirschsprung disease (HSCR) is a congenital disorder of the enteric nervous system (ENS) caused by defective migration of neural crest cells. Genetic factors, including neurotrophic genes such as neurotrophin-3 (NTF3), may contribute to its pathogenesis.
AIM
To investigate the association between the NTF3 rs1805149A>G variant and susceptibility to HSCR in a southern Chinese Han population. In addition, this study also aims to provide population-specific genetic data on HSCR and to explore whether this neurotrophin-related variant contributes to disease pathogenesis, potentially broadening the spectrum of candidate genes implicated in ENS development.
METHODS
A study was conducted involving 1470 HSCR patients and 1473 healthy controls. Genomic DNA was extracted and genotyping of the NTF3 rs1805149 variant was performed using a TaqMan real-time PCR system. Genotype and allele frequencies were analyzed using χ2 tests.
RESULTS
The distribution of genotypes (AA, AG, GG) and allelic frequencies (A and G) showed no statistically significant differences between HSCR patients and controls. No association was found between the rs1805149 variant and specific clinical subtypes of HSCR.
CONCLUSION
The NTF3 rs1805149A>G variant does not appear to be associated with HSCR susceptibility in the studied southern Chinese cohort. Further studies with larger sample sizes and multi-gene analysis are warranted to better understand the genetic basis of HSCR.
Core Tip: This case-control study explores the association between the neurotrophin-3 (NTF3) rs1805149A>G variant and Hirschsprung disease (HSCR) susceptibility in a southern Chinese Han population. Despite previous reports implicating NTF3 in HSCR pathogenesis, no significant association was found in this cohort. The results highlight the complexity of HSCR's genetic architecture and suggest that other factors, such as rare variants or multi-gene interactions, may play a more substantial role in its development. Further studies with larger sample sizes and diverse populations are needed to clarify the genetic basis of HSCR.
