Abstract
Hirschsprung disease (HSCR) is a human birth defect at the clinical setting, usually characterized by an absent enteric nervous system (ENS) from the distal bowel. The majority of HSCR cases represent a complex disorder resulting from the interaction of multiple genetic and environmental factors. Genetic events have been described to be involved in the abnormal development of the enteric nervous system. Although variants in several genes like RET and EDNRB have been suggested to contribute major risks to HSCR, very little is known about their involvement in the onset of HSCR. Here, we studied a large Chinese Han cohort consisting of 1,470 HSCR patients and 1,473 non-HSCR controls to further test whether there are more variants in EDNRB associated with HSCR. Our results provided the first evidence that rs2147555 in EDNRB confers a significant risk of HSCR in a Chinese Han population for both allelic frequencies (P = 4.16 × 10(-3); OR = 1.29) and genotypic frequencies assuming either a dominant or recessive model (P = 0.011 and P = 0.027, respectively). When different subtypes of HSCR cases were analyzed, the association remained significant (OR = 1.33, P = 0.003 for short-segment HSCR; OR = 1.34, P = 0.044 for long segment HSCR).