Polymorphisms of the RET Gene in Hirschsprung Disease, Anorectal Malformation and Intestinal Pseudo-obstruction in Taiwan

Background/Purpose: Mutations in the receptor tyrosine kinase RET gene are associated with Hirschsprung disease (HD), which is also known as congenital intestinal aganglionosis. We found an association with specific alleles in five single nucleotide polymorphism (SNP) sites of the RET gene in our HD patients. Methods: We compared the association of specific RET SNP alleles in patients with severe GI disorders such as anorectal malformation (ARM) or pediatric intestinal pseudo-obstruction (IPO) to that in HD patients. Sixty-four HD, 23 ARM and 35 IPO patients were included. Genomic DNA extracted from blood samples was analyzed by polymerase chain reaction and DNA sequencing analysis. Results: The allele distributions of all five RET SNPs in the HD patients deviated from those in the normal population (p < 0.05), whereas those of the ARM patients did not. The allele distributions of these RET SNPs in the IPO patients were all significantly different from those in the HD patients. Allele distributions of exon 2 and 13 in the IPO patients were also significantly different from those of the normal population. The frequencies of all the HD-predominant alleles were lower in the HD patients than the normal population, and were even lower in the IPO patients. Conclusion: This study strengthens the association of specific RET SNP alleles with typical HD in Taiwan.