Common variants of NRG1 and ITGB4 confer risk of Hirschsprung disease in Han Chinese population

Background Hirschsprung disease (HSCR) is a neurodevelopmental disorder with a strong genetic component. Common variants of NRG1 contributed to HSCR risk in Asians, and rare variants of ERBB2 and ITGB4 were found to be associated with HSCR. ERBB2 and ITGB4 are partners of Nrg1/ErbB pathway, which is important in HSCR pathogenesis. We aimed to investigate whether common variants in NRG1, ERBB2 and ITGB4 were associated with HSCR in Chinese Han population. Methods We genotype 17 single nucleotide polymorphisms (SNPs) of NRG1, ERBB2 and ITGB4 in 420 HSCR patients and 1665 controls, and performed association analysis. Results We validated associations of two NRG1 SNPs rs7835688 (PAllelic = 2.2 × 10− 20, OR = 2.21, 95%CI = 1.86–2.62) and rs16879552 (PAllelic = 5.6 × 10− 9, OR = 1.57, 95%CI = 1.35–1.83) with risk to HSCR. SNP rs3744000 located 5′ upstream of ITGB4 showed association with HSCR (PAllelic = 2.4 × 10− 3, OR = 1.27, 95%CI = 1.09–1.49). Four SNPs of ERBB2 exhibited no association. Conclusions Our results suggested that common variation of ITGB4 and NRG1 conferred risk to HSCR in Chinese Han population, which further highlighted Nrg-1/ErbB pathway involving in the pathogenesis of HSCR. Level of evidence