Pleiotropic effect of common PHOX2B variants in Hirschsprung disease and neuroblastoma

Aging
Jinglu ZhaoYan Zhang

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.

References

Dec 16, 1998·Virchows Archiv : an International Journal of Pathology·C StollU Löhrs
Mar 17, 2004·American Journal of Human Genetics·Delphine TrochetJeanne Amiel
Sep 1, 2004·American Journal of Human Genetics·Yael P MosseJohn M Maris
Nov 2, 2004·Oncogene·Vera van LimptRogier Versteeg
Mar 1, 2005·Oncogene·Patrizia PerriIsabella Ceccherini
Apr 9, 2005·Mechanisms of Development·Stone ElworthyRobert N Kelsh
May 13, 2006·American Journal of Medical Genetics. Part a·Carmel McConvilleNazneen Rahman
Aug 5, 2006·American Journal of Respiratory and Critical Care Medicine·Elizabeth M Berry-KravisDebra E Weese-Mayer
Oct 30, 2007·Journal of Medical Genetics·J AmielUNKNOWN Hirschsprung Disease Consortium
Oct 17, 2008·Nature·Yuyan ChenSeishi Ogawa
Feb 28, 2009·Dementia and Geriatric Cognitive Disorders·Nobuto ShibataHeii Arai
Aug 12, 2009·Pediatric Surgery International·Elke Ruttenstock, Prem Puri
Aug 11, 2011·Pediatric Pulmonology·Lawrence J JenningsDebra E Weese-Mayer
Aug 28, 2012·The Journal of Clinical Investigation·Mayumi NagashimadaHideki Enomoto
Sep 19, 2012·Seminars in Pediatric Surgery·Samuel W Moore
Jan 24, 2013·PloS One·Raquel María FernándezSalud Borrego
May 30, 2013·Nature Genetics·UNKNOWN GTEx Consortium
Aug 16, 2014·International Journal of Cancer. Journal International Du Cancer·Gudrun SchleiermacherOlivier Delattre
Nov 4, 2015·Nucleic Acids Research·Socorro Gama-CastroJulio Collado-Vides
Mar 29, 2016·Journal of Cellular and Molecular Medicine·Jing HeHuimin Xia
Jun 21, 2016·Developmental Biology·A TorroglosaS Borrego
Jan 30, 2018·Journal of Cellular and Molecular Medicine·Yan ZhangHuimin Xia

❮ Previous
Next ❯

Citations

Jul 30, 2019·Clinical Genetics·Berta Luzón-ToroSalud Borrego
May 23, 2020·Pharmacogenomics and Personalized Medicine·Yi ZhengWei Zhong
May 24, 2020·The Journal of Applied Laboratory Medicine·Florette K Hazard, Hiroyuki Shimada
Aug 24, 2021·Frontiers in Pediatrics·Anwarul KarimPaul Kwong-Hang Tam

❮ Previous
Next ❯

Methods Mentioned

BETA
biopsy
surgical resection
genotyping
PCR

Software Mentioned

PLINK
SAS

Related Concepts

Related Feeds

Aging Genetics (Keystone)

This feed focuses on aging epidemiology and genetic, epigenetic, and proteomic aspects underlying aging, as well as aging- associated biomarkers. Here the latest research in this domain.