Background: Hirschsprung disease (HSCR) is a rare congenital gastrointestinal disease characterized by the absence of intestinal submucosal and myometrial ganglion cells. Recently, researches indicated that miR-100  regulated the growth, differentiation and apoptosis of neurons, and affected the functions of HSCR-associated pathways. While miR-100  rs1834306 A>G polymorphism was shown to modify the susceptibility to tumors, the association between this polymorphism and HSCR susceptibility is still unknown.
Methods: This was a case–control study consisting of 1470 HSCR cases and 1473 controls from southern China. DNA was genotyped by TaqMan real-time PCR. Odds ratios (ORs) and 95% confidence intervals (CIs) were used as statistical indicators.
Results: We found that miR-100  rs1834306 G allele and GG genotype significantly increased HSCR susceptibility (GG vs AA: adjusted OR=1.31, 95% CI=1.04– 1.64, P =0.020; G vs A: adjusted OR=1.12, 95% CI=1.01– 1.25, P =0.041; GG vs AA/AG: adjusted OR=1.30, 95% CI=1.07– 1.59, P =0.010). In the stratified analysis, miR-100  rs1834306 GG genotype carriers had higher risk to develop HSCR in all clinical subtypes when compared with those with AA/AG genotypes, and OR was rising with HSCR aggravation (SHSCR: adjusted OR=1.28, 95% CI=1.03– 1.59, P =0.029; LHSCR: adjusted OR=1.48, 95% CI=1.06– 2.07, P =0.020; TCA: adjusted OR=2.12, 95% CI=1.22– 3.69, P =0.008).
Conclusion: Our findings suggested that miR-100  rs1834306 A>G polymorphism was associated with increased HSCR susceptibility in southern Chinese children. Furthermore, miR-100  rs1834306 GG genotype had a greater genetic pathopoiesis in severe HSCR.
Keywords: Hirschsprung disease, miR-100 , polymorphism, susceptibility