Open AccessCommon genetic variants in GAL , GAP 43 and NRSN 1 and interaction networks confer susceptibility to Hirschsprung disease
Author(s) -
Wang Yang,
Yan Weihui,
Wang Jun,
Zhou Ying,
Chen Jie,
Gu Beilin,
Cai Wei
Publication year - 2018
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.13612
Subject(s) - biology , haplotype , genetics , gene , snp , microarray analysis techniques , single nucleotide polymorphism , genotype , gene expression
Hirschsprung disease ( HSCR ) is a severe multifactorial genetic disorder. Microarray studies indicated GAL , GAP 43 and NRSN 1 might contribute to the altered risk in HSCR . Thus, we focused on genetic variations in GAL , GAP 43 and NRSN 1 , and the gene‐gene interactions involved in HSCR susceptibility. We recruited a strategy combining case‐control study and MassArray system with interaction network analysis. For GAL , GAP 43 and NRSN 1 , a total of 18 polymorphisms were assessed in 104 subjects with sporadic HSCR and 151 controls of Han Chinese origin. We found statistically significant differences between HSCR and control groups at 5 genetic variants. For each gene, the haplotypes combining all polymorphisms were the most significant. Based on SNP syn, MDR and Gene MANIA analyses, we observed significant gene‐gene interactions among GAL , GAP 43 , NRSN 1 and our previous identified RELN , GABRG 2 and PTCH 1 . Our study for the first time indicates that genetic variants within GAL , GAP 43 and NRSN 1 and related gene‐gene interaction networks might be involved in the altered susceptibility to HSCR in the Han Chinese population, which might shed more light on HSCR pathogenesis.