PURPOSE: Hirschsprung's disease (HSCR) is characterized by absence of the enteric nervous system in a variable portion of the distal gut. The endothelin receptor type B (EDNRB) gene has been localized to the chromosome 13q22 region and encodes a G-protein coupled receptor, is generally accepted as a crucial gene for HSCR. This study is to identify the epigenetic changes of EDNRB in the pathogenesis of HSCR. METHODS: We investigated the expression levels of EDNRB in 58 HSCR patients and 25 unrelated controls, using reverse transcriptase polymerase chain reaction (RT-PCR) and western blot assay. Moreover, using the methylation-specific polymerase chain reaction, we examined the methylation status of the promoter region of EDNRB. RESULTS: Aberrant high expression level of EDNRB was detected in HSCR patients compared with the control group (P = 0.023). Besides, western blot assay confirmed the up-regulation of EDNRB in the post transcription level in the aganglionosis segment of HSCR patients. Furthermore, there was a significantly lower ratio of methylation level of EDNRB in HSCR. CONCLUSIONS: Our study demonstrates that epigenetic inactivation of the EDNRB gene may play a role in the development of HSCR.
PURPOSE:Hirschsprung's disease (HSCR) is characterized by absence of the enteric nervous system in a variable portion of the distal gut. The endothelin receptor type B (EDNRB) gene has been localized to the chromosome 13q22 region and encodes a G-protein coupled receptor, is generally accepted as a crucial gene for HSCR. This study is to identify the epigenetic changes of EDNRB in the pathogenesis of HSCR. METHODS: We investigated the expression levels of EDNRB in 58 HSCR patients and 25 unrelated controls, using reverse transcriptase polymerase chain reaction (RT-PCR) and western blot assay. Moreover, using the methylation-specific polymerase chain reaction, we examined the methylation status of the promoter region of EDNRB. RESULTS: Aberrant high expression level of EDNRB was detected in HSCR patients compared with the control group (P = 0.023). Besides, western blot assay confirmed the up-regulation of EDNRB in the post transcription level in the aganglionosis segment of HSCR patients. Furthermore, there was a significantly lower ratio of methylation level of EDNRB in HSCR. CONCLUSIONS: Our study demonstrates that epigenetic inactivation of the EDNRB gene may play a role in the development of HSCR.
Authors: Noah R Druckenbrod; Patricia A Powers; Christopher R Bartley; Jeffery W Walker; Miles L Epstein Journal: Genesis Date: 2008-08 Impact factor: 2.487
Authors: Travis P Barr; Daniel Kornberg; Jean-Pierre Montmayeur; Melinda Long; Stephen Reichheld; Gary R Strichartz Journal: Anal Biochem Date: 2014-09-16 Impact factor: 3.365
Authors: Leticia Villalba-Benito; Daniel López-López; Ana Torroglosa; Carlos S Casimiro-Soriguer; Berta Luzón-Toro; Raquel María Fernández; María José Moya-Jiménez; Guillermo Antiñolo; Joaquín Dopazo; Salud Borrego Journal: Clin Epigenetics Date: 2021-03-09 Impact factor: 6.551
Authors: Katherine C MacKenzie; Bianca M de Graaf; Andreas Syrimis; Yuying Zhao; Erwin Brosens; Grazia M S Mancini; Rachel Schot; Dicky Halley; Martina Wilke; Arve Vøllo; Frances Flinter; Andrew Green; Sahar Mansour; Jacek Pilch; Zornitza Stark; Eleni Zamba-Papanicolaou; Violetta Christophidou-Anastasiadou; Robert M W Hofstra; Jan D H Jongbloed; Nayia Nicolaou; George A Tanteles; Alice S Brooks; Maria M Alves Journal: Hum Mutat Date: 2020-09-16 Impact factor: 4.878