title: A common polymorphism in pre-miR-146a underlies Hirschsprung disease risk in Han Chinese.
abstract: BACKGROUND
  Hirschsprung disease (HSCR) is a rare multigenic congenital disorder characterized by the absence of the enteric ganglia. To date, single nucleotide polymorphisms (SNPs) in pre-miRNAs have been confirmed related with some diseases. Thus, we hypothesized that pre-miRNA polymorphisms might contribute to HSCR susceptibility. We investigated whether rs2910164 and rs11614913 of pre-miR-146a and pre-miR-196a2, are associated with HSCR.
  
  
  METHODS
  Polymorphisms were genotyped using the Taqman method. Real-time PCR was used for detecting the expression level of miR-146a and its target gene ROBO1 in CC and GG genotypes.
  
  
  RESULTS
  Significant differences were found in the genotype distribution of rs2910164 and rs11614913 polymorphism between HSCR cases and controls (p = 0.023 and 0.041, respectively). Furthermore, G allele of rs2910164 might increase the risk of HSCR (OR, 1.54; 95% CI, 1.06-2.23). Moreover, the expression level of miR-146a for homozygote GG was also higher than homozygote CC (p = 0.0193). In contrast, the expression level of its target gene ROBO1 predicted in bioinformatics for homozygote GG was much lower than homozygote CC (p = 0.0096).
  
  
  CONCLUSIONS
  Our results showed that the polymorphism rs2910164 in pre-miR-146a might alter the production of mature miR-146a and then down-regulate the target gene ROBO1, which plays an important role in pathogenesis of HSCR.
authors.affiliation: Department of Pediatric Surgery, Nanjing Children's Hospital Affiliated Nanjing Medical University, Nanjing 210008, China; State Key Laboratory of Reproductive Medicine, Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Hairong
authors.initials: H
authors.lastname: Zhu
authors.affiliation: Department of Pediatric Surgery, Nanjing Children's Hospital Affiliated Nanjing Medical University, Nanjing 210008, China; State Key Laboratory of Reproductive Medicine, Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Cai
authors.affiliation: Department of Pediatric Surgery, Nanjing Children's Hospital Affiliated Nanjing Medical University, Nanjing 210008, China; State Key Laboratory of Reproductive Medicine, Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Dongmei
authors.initials: D
authors.lastname: Zhu
authors.affiliation: Department of Pediatric Surgery, Nanjing Children's Hospital Affiliated Nanjing Medical University, Nanjing 210008, China; State Key Laboratory of Reproductive Medicine, Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Xu
authors.affiliation: Department of Pediatric Surgery, Nanjing Children's Hospital Affiliated Nanjing Medical University, Nanjing 210008, China; State Key Laboratory of Reproductive Medicine, Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Hongxing
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Pediatric Surgery, Nanjing Children's Hospital Affiliated Nanjing Medical University, Nanjing 210008, China; State Key Laboratory of Reproductive Medicine, Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Junwei
authors.initials: J
authors.lastname: Tang
authors.affiliation: Department of Pediatric Surgery, Nanjing Children's Hospital Affiliated Nanjing Medical University, Nanjing 210008, China; State Key Laboratory of Reproductive Medicine, Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Xie
authors.affiliation: Key Laboratory of Modern Toxicology (Nanjing Medical University), Ministry of Education, China; State Key Laboratory of Reproductive Medicine, Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Yufeng
authors.initials: Y
authors.lastname: Qin
authors.affiliation: Key Laboratory of Modern Toxicology (Nanjing Medical University), Ministry of Education, China; State Key Laboratory of Reproductive Medicine, Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Ankur
authors.initials: A
authors.lastname: Sharan
authors.affiliation: Department of Pediatric Surgery, Nanjing Children's Hospital Affiliated Nanjing Medical University, Nanjing 210008, China; State Key Laboratory of Reproductive Medicine, Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing 211166, China. Electronic address: twbcn@njmu.edu.cn.
authors.forename: Weibing
authors.initials: W
authors.lastname: Tang
authors.affiliation: Key Laboratory of Modern Toxicology (Nanjing Medical University), Ministry of Education, China; State Key Laboratory of Reproductive Medicine, Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Yankai
authors.initials: Y
authors.lastname: Xia
mesh_terms: D044466:Asian People / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006627:Hirschsprung Disease / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D060888:Real-Time Polymerase Chain Reaction; D011971:Receptors, Immunologic / Q000096:biosynthesis / Q000235:genetics*; D012307:Risk Factors; D000097905:Roundabout Proteins
chemical_list: D035683:MicroRNAs; D009419:Nerve Tissue Proteins; D011971:Receptors, Immunologic; D000097905:Roundabout Proteins; C542542:MIRN146 microRNA, human
keywords: Hirschsprung disease; SNP; pre-miR-146a