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Research Paper|Volume 11, Issue 4|pp 1252—1261

Pleiotropic effect of common PHOX2B variants in Hirschsprung disease and neuroblastoma

Jinglu Zhao1, Yun Zhu1, Xiaoli Xie1, Yuxiao Yao1, Jiao Zhang2, Ruizhong Zhang1, Lihua Huang1, Jiwen Cheng3, Huimin Xia1, Jing He1, Yan Zhang1
  • 1Department of Pediatric Surgery, Guangzhou Institute of Pediatrics, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzho, Guangdong 510623, China
  • 2Department of Pediatric Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzho, Henan 450052, China
  • 3Department of Pediatric Surgery, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'a, Shaanxi 710004, China

* * Equal contribution

Received: December 28, 2018Accepted: February 17, 2019Published: February 22, 2019
https://doi.org/10.18632/aging.101834

Copyright: © 2019 Zhao et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Hirschsprung disease (HSCR) is a heterogeneous congenital disorder that affects the enteric nervous system, while neuroblastoma is an embryonal tumor of the sympathetic nervous system. Familial cases of both HSCR and neuroblastoma appear to be functionally linked to PHOX2B, which plays a key role in the development of neural crest derivatives. However, the association between common PHOX2B variants and disease risk is contested. Additionally, large-scale examination for pleiotropy or shared genetic susceptibility in sporadic HSCR and neuroblastoma cases lacks theoretical support. Here, we report the first examination of PHOX2B in 1470 HSCR and 469 neuroblastoma patients with matched healthy controls. The PHOX2B rs28647582 polymorphism was found to be associated with HSCR (P = 2.21E-03, OR = 1.26), and each subtype of the ailment (3.22E-03 ≤ P ≤ 0.43, 1.11 ≤ OR ≤ 2.32). The association between rs28647582 and NB risk was consistent with HSCR in a recessive model, though the P value was marginal (P = 0.06). These new genetic findings indicate the potential pleiotropic effects of PHOX2B in both HSCR and neuroblastoma, which could guide the development of therapeutic targets for the treatment of related neurodevelopmental disorders.