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.
CONCLUSION: Our results for rs7804122 provided preliminary evidence that the 
SEMA3A gene is involved in the susceptibility to HSCR in the Northeastern 
Chinese population.