title: RET polymorphisms and the risk of Hirschsprung's disease in a Chinese population.
abstract: Hirschsprung's disease (HSCR) is a congenital disorder characterized by intestinal obstructions due to the absence of enteric ganglia along variable lengths of the intestinal tract. RET coding mutations have been found in approximately 50% of familial cases, but they only explain a minority of sporadic cases. Here, we report our investigation of a possible role of RET non-coding mutations in sporadic HSCR patients. The haplotypes of seven single nucleotide polymorphisms (SNPs), all located in a region 4 kb upstream of the gene through to 23 kb of intron 1, and one SNP in exon 2 were constructed in 125 Han Chinese patients with sporadic HSCR and in 148 Han Chinese controls. Our results indicated that eight SNPs were significantly associated with HSCR (P < 0.0001). The C allele of rs2505535 would appear to represent a protecting allele for the Chinese population. One single haplotype composed of these eight markers was present in 59.6% of patients, versus 18.1% of controls. Based on our results, we conclude that non-coding mutations in RET have important roles in the development of HSCR. The unknown functional disease variant(s), with a dosage-dependent effect in HSCR, is likely to be located in the 5'-region of the RET gene.
authors.affiliation: Institute of Cell Biology, Zhejiang University, Hangzhou, Zhejiang, 310058, China.
authors.forename: Cuiping
authors.initials: C
authors.lastname: Liu
authors.affiliation: Institute of Cell Biology, Zhejiang University, Hangzhou, Zhejiang, 310058, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Jin
authors.affiliation: Department of Central Laboratory, Children's Hospital, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Central Laboratory, Children's Hospital, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Jintu
authors.initials: J
authors.lastname: Lou
authors.affiliation: Department of Pediatric Surgery, Taizhou Hospital, Taizhou, China.
authors.forename: Chunfen
authors.initials: C
authors.lastname: Luo
authors.affiliation: Department of Pediatric Surgery, Taizhou Hospital, Taizhou, China.
authors.forename: Xuewu
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Institute of Cell Biology, Zhejiang University, Hangzhou, Zhejiang, 310058, China. lijichen@zju.edu.cn.
authors.forename: Ji-Cheng
authors.initials: JC
authors.lastname: Li
mesh_terms: D002681:China; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005828:Genetics, Population; D006627:Hirschsprung Disease / Q000235:genetics*; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D020641:Polymorphism, Single Nucleotide; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics*; D012307:Risk Factors
chemical_list: D051096:Proto-Oncogene Proteins c-ret