title: SEMA3A rs7804122 polymorphism is associated with Hirschsprung disease in the Northeastern region of China.
abstract: BACKGROUND
  Hirschsprung disease (HSCR) is a congenital disorder characterized by an absence of intrinsic ganglion cells in the nerve plexuses of the lower colon. Our previous results showed increased semaphorin 3A (SEMA3A) expression may be the risk factor for HSCR pathology in a subset of patients. Therefore, the association between polymorphisms in SEMA3A and the risk of HSCR was examined.
  
  
  METHODS
  The genotypes of two SNPs (rs7804122 and rs797821) in the SEMA3A gene in 119 patients with HSCR and 93 controls were examined using PCR-sequencing to determine the contribution of SEMA3A to the HSCR phenotype. PCR reaction with cDNA template was also used to find out whether a novel mutation (Chr7:83634610A→T) influences the SEMA3A pre-mRNA splicing.
  
  
  RESULTS
  Genotypes comprising allele G of rs7804122 (GG or AG) were over-represented in patients (48.74 vs. 24.8%; p = 0.0013) which indicated that the risk of HSCR was significantly higher among subjects with the GG or AG genotype than among the subjects with the AA genotype. No statistically significant associations were found for SNP rs797821 at the allele or genotype levels. The differences in genotypes and allele distributions of rs7804122 and rs797821 between various clinical classifications were not statistically significant. The novel heterozygous mutation (Chr7:83634610A→T) 30bp away from an intron/exon boundary, had no detectable effect on splicing efficiency.
  
  
  CONCLUSIONS
  Our results for rs7804122 provided preliminary evidence that the SEMA3A gene is involved in the susceptibility to HSCR in the Northeastern Chinese population.
authors.affiliation: Key Laboratory of Health Ministry for Congenital Malformation, Shengjing Hospital, China Medical University, Shenyang 110004, People's Republic of China.
authors.forename: Li-Li
authors.initials: LL
authors.lastname: Wang
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.forename: Yang
authors.initials: Y
authors.lastname: Fan
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.forename: Feng-Hua
authors.initials: FH
authors.lastname: Zhou
authors.forename: Jia-Ning
authors.initials: JN
authors.lastname: Miao
authors.forename: Hui
authors.initials: H
authors.lastname: Gu
authors.forename: Tian-Chu
authors.initials: TC
authors.lastname: Huang
authors.forename: Zheng-Wei
authors.initials: ZW
authors.lastname: Yuan
mesh_terms: D044466:Asian People / Q000235:genetics*; D002681:China; D005091:Exons / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006579:Heterozygote; D006627:Hirschsprung Disease / Q000208:ethnology / Q000235:genetics*; D006801:Humans; D007438:Introns / Q000235:genetics; D008297:Male; D009154:Mutation; D020641:Polymorphism, Single Nucleotide; D040121:Semaphorin-3A / Q000235:genetics*
chemical_list: D040121:Semaphorin-3A