title: Genetic variants of IL-11 associated with risk of Hirschsprung disease.
abstract: BACKGROUND
  Hirschsprung disease (HSCR) is a congenital and heterogeneous disorder characterized by the absence of enteric ganglia during enteric nervous system (ENS) development. Our recent genome-wide association study has identified a variant (rs6509940) of interleukin-11 (IL-11) as a potential susceptible locus for HSCR. As interleukins play important roles in the ENS, we further studied associations with HSCR of nine common single nucleotide polymorphisms (SNPs) on IL-11.
  
  
  METHODS
  Biopsy specimens or surgical materials from all patients that were tested for histological examination based on the absence of the enteric ganglia were collected. A total of nine SNPs on IL-11 were genotyped in 187 HSCR patients and 283 unaffected controls using TaqMan genotyping assay.
  
  
  RESULTS
  Combined analysis revealed that several SNPs (minimum p = 1.57 × 10(-7) ) showed statistically significant associations with HSCR, even after Bonferroni correction (pcorr  = 1.73 × 10(-6) for the SNP). Moreover, the most common haplotype was strongly associated with HSCR (pcorr  = 2.20 × 10(-6) ). In further analysis among three HSCR subtypes (short segment, S-HSCR; long segment, L-HSCR; total colonic aganglionosis, TCA) based on the extent of aganglionic segment, the result showed a different association pattern depending on the subtypes (minimum pcorr  = 6.12 × 10(-5) for rs6509940 in S-HSCR; but no significant SNP in L-HSCR and TCA).
  
  
  CONCLUSIONS
  Although further replication in a larger cohort and functional evaluations are needed, our findings suggest that genetic variations of IL-11 may be associated with the risk of HSCR and/or the mechanisms related to ENS development.
authors.affiliation: Department of Life Science, Sogang University, Seoul, Korea.
authors.forename: L H
authors.initials: LH
authors.lastname: Kim
authors.affiliation: Department of Genetic Epidemiology, SNP Genetics, Inc., Seoul, Korea.
authors.forename: H S
authors.initials: HS
authors.lastname: Cheong
authors.affiliation: Department of Life Science, Sogang University, Seoul, Korea.
authors.forename: J-G
authors.initials: JG
authors.lastname: Shin
authors.affiliation: Division of Pediatric Surgery, Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: J-M
authors.initials: JM
authors.lastname: Seo
authors.affiliation: Department of Pediatric Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: D-Y
authors.initials: DY
authors.lastname: Kim
authors.affiliation: Department of Pediatric Surgery, Severance Children's Hospital, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: J-T
authors.initials: JT
authors.lastname: Oh
authors.affiliation: Department of Pediatric Surgery, Seoul National University Children's Hospital, Seoul, Korea.
authors.forename: H-Y
authors.initials: HY
authors.lastname: Kim
authors.affiliation: Department of Surgery, Seoul National University Bundang Hospital, Seongnam, Gyeonggi, Korea.
authors.forename: K
authors.initials: K
authors.lastname: Jung
authors.affiliation: Department of Physiology, College of Medicine, Hanyang University, Seoul, Korea.
authors.forename: I
authors.initials: I
authors.lastname: Koh
authors.affiliation: Research Institute for Basic Science, Sogang University, Seoul, Korea.
authors.forename: J-H
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Life Science, Sogang University, Seoul, Korea.|Research Institute for Basic Science, Sogang University, Seoul, Korea.
authors.forename: H D
authors.initials: HD
authors.lastname: Shin
mesh_terms: D017615:Enteric Nervous System / Q000002:abnormalities*; D005260:Female; D006239:Haplotypes; D006627:Hirschsprung Disease / Q000235:genetics*; D006801:Humans; D017370:Interleukin-11 / Q000235:genetics*; D008297:Male; D020641:Polymorphism, Single Nucleotide
chemical_list: C508611:IL11 protein, human; D017370:Interleukin-11
keywords: Hirschsprung; IL-11; enteric nervous system; haplotype; single nucleotide polymorphism