miR-100 rs1834306 A>G Increases the Risk of Hirschsprung Disease in Southern Chinese Children

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.

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.

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).

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.