Aberrant UBR4 expressions in Hirschsprung disease patients

Background Recently, pathogenic alleles within ubiquitin N-recognin domain-containing E3 ligase 4 (UBR4) gene have been shown to be associated with Hirschsprung disease (HSCR). We determined the UBR4 expressions in Indonesian HSCR patients. Methods We analyzed the UBR4 expressions in the colons of HSCR patient and anorectal malformation (ARM) patient as control by real-time polymerase chain reaction (qPCR). Results Thirty-seven patients with non-syndromic HSCR and eighteen controls were involved in this study. qPCR revealed that the UBR4 expression was strongly decreased (0.77-fold) in the ganglionic group of patients with HSCR compared to the control group with ARM (ΔCT 2.43 ± 0.36 vs. 2.05 ± 0.69; p = 0.009), whereas the UBR4 expression was also significantly reduced (0.79-fold) in the aganglionic group of patients with HSCR compared to the control group with ARM (ΔCT 2.39 ± 0.46 vs. 2.05 ± 0.69; p = 0.044). However, the UBR4 expression change was not associated with gender (p = 0.35 and 0.80), nor with degree of aganglionosis both in ganglionic and aganglionic colons (p = 0.72 and 0.73), respectively. Conclusion Our study demonstrates that expression of UBR4 is decreased in both aganglionic and ganglionic colon of HSCR patients.

Higher G allele frequency of RET C2307t>G polymorphism in female patients with Hirschsprung disease in Yogyakarta, Indonesia

Background Hirschsprung disease (HSCR) is a heterogenouscongenital disorder and the current research show that the RETgene is a major locus involved in its pathogenesis. However,whether these genes take a part in sporadically Indonesian HSCRhave not been fully understood.Objective The aim of this study was to analyze the association ofRET gene c2307T>G polymorphism among HSCR patient inYogyakarta population.Methods Genomic DNA was extracted from bowel tissues of 34patients with sporadic HSCR which were removed by surgery ascase group and blood DNA from 46 healthy persons as controlgroup without history of genetic disorder. Exon 13 of RET genewas amplified by polymerase chain reaction (PCR) and wasanalyzed by restriction fragment length polymorphism (RFLP).Results Of 34 patients, 22 were males and 12 were females, givingmale to female ratio of 1.83:1. The c2307T>G polymorphism inRET exon 13 was not significantly difference between patientand control group (chi-square test P=0.17). However, there wasa significant difference in female patient compare with control(chi-square test P=0,04).Conclusion The RET gene c2307T>G polymorphism was foundamong HSCR patient in Yogyakarta population. This poly-morphism can be used as predictor for development of HSCRamong female individual.