A common polymorphism in pre-miR-146a underlies Hirschsprung disease risk in Han Chinese.

BACKGROUND

Hirschsprung disease (HSCR) is a rare multigenic congenital disorder characterized by the absence of the enteric ganglia. To date, single nucleotide polymorphisms (SNPs) in pre-miRNAs have been confirmed related with some diseases. Thus, we hypothesized that pre-miRNA polymorphisms might contribute to HSCR susceptibility. We investigated whether rs2910164 and rs11614913 of pre-miR-146a and pre-miR-196a2, are associated with HSCR.

METHODS

Polymorphisms were genotyped using the Taqman method. Real-time PCR was used for detecting the expression level of miR-146a and its target gene ROBO1 in CC and GG genotypes.

RESULTS

Significant differences were found in the genotype distribution of rs2910164 and rs11614913 polymorphism between HSCR cases and controls (p = 0.023 and 0.041, respectively). Furthermore, G allele of rs2910164 might increase the risk of HSCR (OR, 1.54; 95% CI, 1.06-2.23). Moreover, the expression level of miR-146a for homozygote GG was also higher than homozygote CC (p = 0.0193). In contrast, the expression level of its target gene ROBO1 predicted in bioinformatics for homozygote GG was much lower than homozygote CC (p = 0.0096).

CONCLUSIONS

Our results showed that the polymorphism rs2910164 in pre-miR-146a might alter the production of mature miR-146a and then down-regulate the target gene ROBO1, which plays an important role in pathogenesis of HSCR.