title: WNT3A gene expression is associated with isolated Hirschsprung disease polymorphism and disease status.
abstract: WNT3A has been regarded as an activator of the canonical Wnt signaling pathway. It has been found Wnt signaling pathway is closely related with embrionic development and Hirschsprung disease (HSCR). A common haplotype consisting of minor SNPs alleles located in the WNT3A gene has been described as a risk factor for various genetic disorders. However, whether WNT3A contributes to the onset of HSCR has not been identified. The present study aims to detect the interactions of genetic variations in the WNT3A gene and examine the biological expression levels with Hirschsprung disease (HSCR) in the Chinese people. We analyzed WNT3A gene (rs61743220, rs192966556 and rs145882986) variants in the whole blood samples from HSCR patients and normal children (control groups). WNT3A expression was also examined by quantitative real-time PCR (qRT-PCR), western blotting and immunostaining. Consequently, when rs192966556 and rs145882986 alleles of the WNT3A gene lack the SNPs, they are especially associated with a greater risk of HSCR (OR [95% confidence interval]=1.791, p=0.001; OR [95% confidence interval]=1.556, p=0.003, respectively). The mRNA and protein expressions of WNT3A were higher in the aganglionic colon segment tissues than in the normal ganglionic segments tissues. Immunostaining indicates that the staining of WNT3A was much stronger (brown) in the aganglionic colon segment tissues than that in the normal ganglionic colon segment tissues (colorless or light yellow) in the mucous layer and muscular layer. Although preliminary, these results suggest that WNT3A may play an important role in the pathogenesis of HSCR.
authors.affiliation: Department of Pediatric Surgery, Shengjing Hospital of China Medical University Shenyang 110004, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Chen
authors.affiliation: Department of Pediatric Surgery, Shengjing Hospital of China Medical University Shenyang 110004, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Mi
authors.affiliation: Key Laboratory of Pediatric Congenital Malformations, Ministry of Public Health, Shengjing Hospital of China Medical University Shenyang 110004, China.
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Liu
authors.affiliation: Jinzhou Women and Children's Hospital Jinzhou, Liaoning, 121000, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Pediatric Surgery, Shengjing Hospital of China Medical University Shenyang 110004, China.
authors.forename: Weilin
authors.initials: W
authors.lastname: Wang
authors.affiliation: Key Laboratory of Pediatric Congenital Malformations, Ministry of Public Health, Shengjing Hospital of China Medical University Shenyang 110004, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Gao
mesh_terms: D000483:Alleles; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D002675:Child, Preschool; D002681:China; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006627:Hirschsprung Disease / Q000175:diagnosis* / Q000235:genetics* / Q000503:physiopathology; D006801:Humans; D007223:Infant; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D017422:Sequence Analysis, DNA; D012720:Severity of Illness Index; D060449:Wnt Signaling Pathway / Q000502:physiology; D060509:Wnt3A Protein / Q000235:genetics* / Q000502:physiology
chemical_list: C555510:WNT3A protein, human; D060509:Wnt3A Protein
keywords: Hirschsprung disease; WNT3A; expression; gene and protein; polymorphism