Hedgehog gene polymorphisms are associated with the risk of Hirschsprung's disease and anorectal malformation in a Chinese population.

Hedgehog (HH) is one of the key morphogens expressed in the gut mesenchyme that control animal development and tissue homeostasis. The HH gene has been shown to be closely associated with Hirschsprung's disease (HSCR) and anorectal malformations (ARMs); thus, it was hypothesized that HH signaling pathway‑associated genes may be candidate genes for HSCR and ARMs. The present study aimed to evaluate whether polymorphisms in the HH gene were associated with HSCR and ARM in a Chinese population. HH gene variants (rs61730970, rs200798148 and rs146535482) were analyzed in whole blood samples from patients with HSCR and ARMs, as well as normal children (control group). The results suggested that, when the rs61730970, rs200798148 and rs146535482 alleles of the HH gene lacked particular single nucleotide polymorphisms (SNPs), the patients were associated with a greater risk of HSCR and/or ARM [HSCR: odds ratio (OR)=1.543, P=0.004; OR=1.494, P=0.007; rs146535482: OR=1.556, P=0.003, respectively. ARM: OR=1.528, P=0.045; OR=1.800, P=0.007; OR=1.743, P=0.009, respectively). Sequencing of rs61730970 and rs200798148 revealed a loss of heterozygosity and SNPs at these loci in patients with HSCR. Similarly, the sequencing of rs61730970 and rs146535482 revealed a loss of heterozygosity and SNPs at these loci in patients with ARM. Although preliminary, these results suggested that the HH gene may be involved in genetic interactions associated with the pathogenesis of HSCR and ARM.