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.
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Acknowledgments
This work was supported by National Found for Fostering Talents of Basic Science (No.J0730856) and the Medical Science Foundation of Zhejiang Province (No. 2002A027).
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Liu, C., Jin, L., Li, H. et al. RET polymorphisms and the risk of Hirschsprung’s disease in a Chinese population. J Hum Genet 53, 825–833 (2008). https://doi.org/10.1007/s10038-008-0315-x
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DOI: https://doi.org/10.1007/s10038-008-0315-x
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