Polymorphisms and expression of the WNT8A gene in Hirschsprung's disease.

Hirschsprung's disease (HSCR) is a congenital disorder characterized by an absence of intrinsic ganglion cells in the nerves forming the plexus of the lower intestine. The WNT signaling pathway is considered to play an important role in embryonic development. In the present study, we analyzed 2 polymorphisms of the WNT8A gene (rs78301778 and rs6596422) to determine their association with the risk and development of HSCR. Allele frequencies and genotype distributions were analyzed by sequence analysis in patients with HSCR and normal controls. Using real-time PCR, western blot analysis and immunohistochemistry, we detected the mRNA and protein expression of WNT8A in patients with HSCR. The data indicated that the differences in genotype distributions and allele frequencies of rs78301778 and rs6596422 between various clinical classifications were statistically significant. The analysis of the mRNA and protein expression of WNT8A revealed that the expression of WNT8A was increased in the stenotic colon segments compared with the normal colon segments. In conclusion, the data presented in this study suggest that the WNT8A gene is involved in the susceptibility to HSCR, and plays an important role in the occurrence and development of HSCR. These findings warrant further investigation.