Genotyping analysis of 3 RET polymorphisms demonstrates low somatic mutation rate in Chinese Hirschsprung disease patients

Zhen Zhang, Qian Jiang, Qi Li, Wei Cheng, Guoliang Qiao, Ping Xiao, Liang Gan, Lin Su, Chunyue Miao, Long Li

Research output: Contribution to journalArticlepeer-review


Background: Genetic mosaicism has been reported for both coding and non-coding sequences in the RET gene in Hirschsprung disease (HSCR) patients. This study aimed to investigate somatic mutation rate in Chinese population by comparing both homozygous genotype percentage and risk allele frequency of 3 RET single nucleotide polymorphisms (SNPs) among blood and colon samples. Methods: DNA was extracted from 59 HSCR blood samples, 59 control blood samples and 76 fresh frozen colon tissue samples (grouped into ganglionic, transitional and aganglionic level). Genotype status of rs2435357 and rs2506030 was examined by competitive allele specific hydrolysis probes (Taqman) PCR technology, and rs2506004 was examined by Sanger sequencing. Homozygous genotype percentage and risk allele frequency were calculated for each type of sample and compared by chi-square test. P<0.05 was regarded as being statistically significant. Results: Colon tissue DNA samples showed similar frequency of SNPs as that of the blood DNA samples in HSCR patients, both of which are significantly higher than the control blood group (rs2435357 TT genotype: 71.2%, 74.7% versus 22.0% in HSCR blood, HSCR colon and control blood DNA respectively, P=0.000; rs2506004 AA genotype: 72.4%, 83.1% versus 25.5%, P=0.000; rs2506030 GG genotype: 79.7%, 77.2% versus 54.2%, P=0.000 and 0.004). With respect to DNA extracted from ganglionic, transitional and aganglionic levels, no statistically significant difference was demonstrated in those 3 regions (rs2435357: P=0.897; rs2506004: P=0.740; rs2506030: P=0.901). Conclusion: Our data does not support the notion that high frequency of somatic changes as an underlying etiology of Chinese HSCR population.

Original languageEnglish (US)
Pages (from-to)5528-5534
Number of pages7
JournalInternational Journal of Clinical and Experimental Pathology
Issue number5
StatePublished - 2015
Externally publishedYes


  • Fresh frozen colon
  • Genetic mosaicism
  • Hirschsprung disease
  • RET proto-oncogene

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Histology

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