New variations of the EDNRB gene and its association with sporadic Hirschsprung's disease in Korea

Background/Purpose: The endothelin receptor B (EDNRB) signaling pathway, which is the second major susceptible gene for Hirschsprung's disease (HSCR), is crucial for the development of the enteric nervous system. The allele frequency of polymorphisms was mostly tested in the American and European population, but the data of an ethnically diverse, non-Caucasian population are unclear. To further investigate the variants and haplotypes of the EDNRB gene, this study examined sequence variations in Korean patients with sporadic HSCR. Methods: All 8 exons and intron/exon boundaries of the EDNRB gene in 18 Korean patients with sporadic HSCR and 84 healthy individuals were screened using PCR amplification and direct sequencing. Results: A total of 8 different nucleotide substitutions were identified. Of these, 4 were new variants (promoter-116C>T; 5′UTR-121G>T; IVS4+62C>A; IVS5+121G>C) and the others were previously described variants. The distribution of variations was even different from that reported for Chinese and Japanese subjects as well as other ethnic groups. This study also analyzed the haplotypes for an association between the variants identified with HSCR. Conclusions: This study identified additional sequence variants of the EDNRB gene, but the estimated EDNRB haplotypes did not show any disease risk.