Supplementary Material for: Potential Association of INMT Nonsynonymous Variant (His46Pro) with Hirschsprung's Disease

Background: Hirschsprung's disease (HSCR) is a congenital disorder which is characterized by the lack of ganglion cells in part of or the entire colon, resulting in intestinal obstruction and other related symptoms. Recently, our group has conducted a genome-wide association study in Korean HSCR cases and controls to identify novel markers in other genes. Objectives: The present research aimed to further study the potential association of INMT with HSCR by conducting a replication study. Methods: A total of 15 INMT single nucleotide polymorphisms (SNPs) were analyzed for the association with HSCR in 187 HSCR patients and 283 controls. Analyses were also conducted for subtypes of HSCR (short-segment, long-segment, and total colonic aganglionosis). Results: A nonsynonymous SNP rs77743549 (His46Pro) was significantly associated with the increased risk of HSCR (odds ratio = 1.77; corrected p = 0.002). Furthermore, this rs77743549 retained its association with all subtypes of HSCR (p = 0.006-0.002 under the codominant model). A global test showed that rs77743549 was associated with the length of aganglionosis (p = 0.00004). Conclusion: Although further replications and functional evaluations are needed, our study suggests that rs77743549 of INMT may be associated with the risk for HSCR and/or the development of the enteric nervous system.