Research Paper Volume 10, Issue 4 pp 689—700

Association of VAMP5 and MCC genetic polymorphisms with increased risk of Hirschsprung disease susceptibility in Southern Chinese children

Jinglu Zhao1, *,, Xiaoli Xie1, *,, Yuxiao Yao1, *,, Qiuming He1, , Ruizhong Zhang1, , Huimin Xia1, , Yan Zhang1, ,

  • 1 Department of Pediatric Surgery, Guangzhou Institute of Pediatrics, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzho, Guangdong 510623, China
* Equal contribution

Received: January 2, 2018       Accepted: April 20, 2018       Published: April 25, 2018
How to Cite

Copyright: 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.


Hirschsprung disease (HSCR) is a genetic disorder characterized by the absence of neural crest cells in parts of the intestine. This study aims to investigate the association of vesicle-associated membrane protein 5 (VAMP5) and mutated in colorectal cancer (MCC) genetic polymorphisms and their correlated risks with HSCR. We examined the association in four polymorphisms (rs10206961, rs1254900 and rs14242 in VAMP5, rs11241200 in MCC) and HSCR susceptibility in a Southern Chinese population composed of 1473 cases and 1469 controls. Two variants in VAMP5 were replicated as associated with HSCR. Interestingly, we clarified SNPs rs10206961 and rs1254900 in VAMP5 are more essential for patients with long-segment aganglionosis (LHSCR). Relatively high expression correlation was observed between VAMP5 and MCC using data from public database showing there may exist potential genetic interactions. SNP interaction was cross-examined by logistic regression and multifactor dimensionality reduction analysis revealing that VAMP5 rs1254900 and MCC rs11241200 were interacting significantly, thereby contributing to the risk of HSCR. The results suggest that significant associations of the rs10206961 and rs14242 in VAMP5 with an increased risk of HSCR in Southern Chinese, especially in LHSCR patients. This study provided new evidence of epistatic association of VAMP5 and MCC with increased risk of HSCR.


BA: Balanced accuracy; CEU: northern and western Europe; CMH: Cochran-Mantel-Haenszel; CRC: colorectal cancer; CV: cross-validation; ENS: enteric nervous system; GLUT-4: glucose transporter type 4; GWAS: genome-wide association study; HSCR: Hirschsprung disease; HWE: hardy-weinberg equilibrium; LD: Linkage disequilibrium; L-HSCR: long-segment HSCR; MCC: Mutated in colorectal cancer; OR: odds ratios; MDR: multifactor dimensionality reduction; S-HSCR: short-segment HSCR; SNARE: soluble NSF attachment protein receptor; SNPs: Single nucleotide polymorphisms; TCA: total colonic aganglionosis; VAMP5: vesicle-associated membrane protein 5.