Associations Between Genetic Polymorphisms In RET And Risk Of Hirschsprung’s Disease

Objective:Hirschsprung’s Disease (HSCR), also known as intestinal ganglion celldisorder which is a common congenital malformation of the gastrointestinal in children. It is morbidity in the second place with congenital digestive tract malformations Charaeterized by the absence of the bowel myenteric plexus and submucosal plexus ganglion cells. The present study proved that it is a kind of multi-genotype disease.It is the result of the interaction of multiple genetic loci, the most important gene is the RET proto-oncogene.RET gene polymorphisms and haplotypes Including disease-related gene mutations may be works as a modifying factors which is associated with the increase risk of the neural crest embryo cell development disorder.The aim of this study analyzed single nucleotide polymorphisms in the RET proto-neogen intronl C> T(rs2435357) and their correlations with the etiopathogenisis of HSCR.Methods:115blood samples were exacted fromthe patients who were diagnosed and reated in Shenzhen Children’s Hospital between May.2008and Aug.2011.The patients aged from17days to81days (90men,25women,4TCA,6L-HSCR,105S-HSCR), who were all sporadic and nor HSCR hereditary history.All patients were eonfirmed HSCR by pathological diagnose.Venous whole blood samples was collected from139sex-and age-matched normal children from Shenzhen Children’s Hospital medical as a control group.Genomie DNA was extracted from whole blood samples by QIAamp-Blood Kit Polymerase Chain Reaction (polymerase chain reaction,PCR amplified in the intron1(rs2435357) of the RET Proto-ncogene.Single-ucleotide polymorphisms were analyzed by direct DNA sequencing.Then, we detect the difference between the allele in two groups. Associations with risk of HSCR were estimated by odds ratio (OR) and their95%confidence intervals (95%CI) using logistic regression.Results:The genotype frequency distribution of RET intronlC> T (rs2435357)was significantly different(P<0.001).Risk of HSCR associated with homozygous genotypes of the RET intronlTT was found compared with the RET intronlCC genotypes (OR=19.22,95%CI.7.54-48.99).Conclusion:These findings suggest that RETpolymorphism RET intronlC> T(rs2435357) may be a genetic susceptibility factor for HSCR in Shenzhen region.