OBJECTIVETo investigate the association of Axis inhibitor-2 (AXIN2) gene rs2240308, rs8081536 and rs9913621 single nucleotide polymorphisms (SNPs) with Hirschsprung disease(HSCR).

METHODSDNA was extracted from 120 HSCR patients and 120 healthy controls. The AXIN2 gene exon2-rs2240308, exon5- rs8081536 and exon6-rs9913621 were amplified by polymerase chain reaction (PCR). SNPs of AXIN2 gene were analyzed by restrictive endonuclease digestion with CviJI, DdeI and BstNI and DNA sequencing. The allele and genotype frequencies and risk factors of HSCR and control group were analyzed by Chi-square test.

RESULTSNo significant differences were found in genotype frequencies of CC and CT in AXIN2 rs8081536 between HSCR patients and the control group (P> 0.05). The frequencies of genotypes GG, AG and AA as well as alleles A and G genotypes in AXIN2 gene rs2240308 locus were found to be associated with HSCR (P< 0.05). The disease risk of genotypes GG and AA and allele G with was 2.091, 0.846 and 1.703, respectively. The frequencies of genotypes CC, CT and TT as well as alleles C and T in AXIN2 gene rs9913621 locus were also associated with HSCR (P< 0.05). The disease risk of the genotypes CC and TT and the allele T was 0.535, 1.113 and 1.569, respectively. Heterozygote mutation for rs2240308 was found in the HSCR patients, i.e. the GCA to CCA mutation at position 301. Heterozygosity for rs9913621 was observed in the HSCR patients, i.e. the CAC to CAG mutation at position 199.

CONCLUSIONThe rs8081536 allelic variation in AXIN2 gene does not contribute to the susceptibility of HSCR in the patients. AXIN2 rs2240308 and rs9913621 allelic variation might be related to HSCR. Individuals having allele G and T in these loci are at relatively high risk for HSCR.