rs1834306 A>G Increases the Risk of Hirschsprung Disease in Southern Chinese Children.

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 regulated the growth, differentiation and apoptosis of neurons, and affected the functions of HSCR-associated pathways. While 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 rs1834306 G allele and GG genotype significantly increased HSCR susceptibility (GG vs AA: adjusted OR=1.31, 95% CI=1.04-1.64, =0.020; G vs A: adjusted OR=1.12, 95% CI=1.01-1.25, =0.041; GG vs AA/AG: adjusted OR=1.30, 95% CI=1.07-1.59, =0.010). In the stratified analysis, 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, =0.029; LHSCR: adjusted OR=1.48, 95% CI=1.06-2.07, =0.020; TCA: adjusted OR=2.12, 95% CI=1.22-3.69, =0.008).

CONCLUSION

Our findings suggested that rs1834306 A>G polymorphism was associated with increased HSCR susceptibility in southern Chinese children. Furthermore, rs1834306 GG genotype had a greater genetic pathopoiesis in severe HSCR.