The impact of NRG1 expressions and methylation on multifactorial Hirschsprung disease
Background: Hirschsprung disease (HSCR) is a complex genetic disorder characterized by the lack of ganglion cells in the intestines. A current study showed that the NRG1 rare variant frequency in Indonesian patients with HSCR is only 0.9%. Here, we investigated the impact of NRG1 expressions and met...
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| Format: | Article |
| Language: | English |
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BioMed Central Ltd
2022
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| Online Access: | https://repository.ugm.ac.id/283809/1/238.pdf |
| _version_ | 1826050693161549824 |
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| author | Gunadi, Gunadi Kalim, Alvin Santoso Marcellus, Marcellus Budi, Nova Yuli Prasetyo Iskandar, Kristy |
| author_facet | Gunadi, Gunadi Kalim, Alvin Santoso Marcellus, Marcellus Budi, Nova Yuli Prasetyo Iskandar, Kristy |
| author_sort | Gunadi, Gunadi |
| collection | UGM |
| description | Background: Hirschsprung disease (HSCR) is a complex genetic disorder characterized by the lack of ganglion cells in the intestines. A current study showed that the NRG1 rare variant frequency in Indonesian patients with HSCR is only 0.9%. Here, we investigated the impact of NRG1 expressions and methylation patterns on the pathogenesis of HSCR. Methods: This cross-sectional study determined NRG1 type I (HRGα, HRGβ1, HRGβ2, HRGβ3, HRGγ, and NDF43 isoforms), type II and type III expressions in both ganglionic and aganglionic colons of 20 patients with HSCR and 10 control colons by real-time polymerase chain reaction (qPCR). For methylation studies, we treated the extracted gDNA from 16 HSCR patients’ and 17 control colons with sodium bisulfate and analyzed the methylation pattern of NRG1 exon 1 with methylation-specific PCR. The samples were collected and analyzed at our institution from December 2018 to December 2020. Results: NRG1 types I, II and III expressions were upregulated (17.2-, 3.2-, and 7.2-fold, respectively) in the ganglionic colons compared with control colons (type I: 13.32 ± 1.65 vs. 17.42 ± 1.51, p < 0.01; type II: 13.73 ± 2.02 vs. 16.29 ± 2.19, p < 0.01; type III: 13.47 ± 3.01 vs. 16.32 ± 2.58, p = 0.03; respectively); while only type I (7.7-fold) and HRGβ1/HRGβ2 (3.3-fold) isoforms were significantly upregulated in the aganglionic colons compared to the controls (type I: 14.47 ± 1.66 vs. 17.42 ± 1.51, p < 0.01; HRGβ1/HRGβ2: 13.62 ± 3.42 vs 14.75 ± 1.26, p = 0.01). Moreover, the frequency of partially methylated NRG1 was higher in the ganglionic (81%) and aganglionic (75%) colons than in the controls (59%). Conclusions: Our study provides further insights into the aberrant NRG1 expression in the colons of patients with HSCR, both ganglionic and aganglionic bowel, which might contribute to the development of HSCR, particularly in Indonesia. Furthermore, these aberrant NRG1 expressions might be associated with its methylation pattern. © 2022, The Author(s). |
| first_indexed | 2024-03-14T00:08:37Z |
| format | Article |
| id | oai:generic.eprints.org:283809 |
| institution | Universiti Gadjah Mada |
| language | English |
| last_indexed | 2024-03-14T00:08:37Z |
| publishDate | 2022 |
| publisher | BioMed Central Ltd |
| record_format | dspace |
| spelling | oai:generic.eprints.org:2838092023-11-22T08:22:30Z https://repository.ugm.ac.id/283809/ The impact of NRG1 expressions and methylation on multifactorial Hirschsprung disease Gunadi, Gunadi Kalim, Alvin Santoso Marcellus, Marcellus Budi, Nova Yuli Prasetyo Iskandar, Kristy Paediatrics Background: Hirschsprung disease (HSCR) is a complex genetic disorder characterized by the lack of ganglion cells in the intestines. A current study showed that the NRG1 rare variant frequency in Indonesian patients with HSCR is only 0.9%. Here, we investigated the impact of NRG1 expressions and methylation patterns on the pathogenesis of HSCR. Methods: This cross-sectional study determined NRG1 type I (HRGα, HRGβ1, HRGβ2, HRGβ3, HRGγ, and NDF43 isoforms), type II and type III expressions in both ganglionic and aganglionic colons of 20 patients with HSCR and 10 control colons by real-time polymerase chain reaction (qPCR). For methylation studies, we treated the extracted gDNA from 16 HSCR patients’ and 17 control colons with sodium bisulfate and analyzed the methylation pattern of NRG1 exon 1 with methylation-specific PCR. The samples were collected and analyzed at our institution from December 2018 to December 2020. Results: NRG1 types I, II and III expressions were upregulated (17.2-, 3.2-, and 7.2-fold, respectively) in the ganglionic colons compared with control colons (type I: 13.32 ± 1.65 vs. 17.42 ± 1.51, p < 0.01; type II: 13.73 ± 2.02 vs. 16.29 ± 2.19, p < 0.01; type III: 13.47 ± 3.01 vs. 16.32 ± 2.58, p = 0.03; respectively); while only type I (7.7-fold) and HRGβ1/HRGβ2 (3.3-fold) isoforms were significantly upregulated in the aganglionic colons compared to the controls (type I: 14.47 ± 1.66 vs. 17.42 ± 1.51, p < 0.01; HRGβ1/HRGβ2: 13.62 ± 3.42 vs 14.75 ± 1.26, p = 0.01). Moreover, the frequency of partially methylated NRG1 was higher in the ganglionic (81%) and aganglionic (75%) colons than in the controls (59%). Conclusions: Our study provides further insights into the aberrant NRG1 expression in the colons of patients with HSCR, both ganglionic and aganglionic bowel, which might contribute to the development of HSCR, particularly in Indonesia. Furthermore, these aberrant NRG1 expressions might be associated with its methylation pattern. © 2022, The Author(s). BioMed Central Ltd 2022 Article PeerReviewed application/pdf en https://repository.ugm.ac.id/283809/1/238.pdf Gunadi, Gunadi and Kalim, Alvin Santoso and Marcellus, Marcellus and Budi, Nova Yuli Prasetyo and Iskandar, Kristy (2022) The impact of NRG1 expressions and methylation on multifactorial Hirschsprung disease. BMC Pediatrics, 22 (1). p. 216. ISSN 14712431 https://link.springer.com/content/pdf/10.1186/s12887-022-03287-1.pdf 10.1186/s12887-022-03287-1 |
| spellingShingle | Paediatrics Gunadi, Gunadi Kalim, Alvin Santoso Marcellus, Marcellus Budi, Nova Yuli Prasetyo Iskandar, Kristy The impact of NRG1 expressions and methylation on multifactorial Hirschsprung disease |
| title | The impact of NRG1 expressions and methylation on multifactorial Hirschsprung disease |
| title_full | The impact of NRG1 expressions and methylation on multifactorial Hirschsprung disease |
| title_fullStr | The impact of NRG1 expressions and methylation on multifactorial Hirschsprung disease |
| title_full_unstemmed | The impact of NRG1 expressions and methylation on multifactorial Hirschsprung disease |
| title_short | The impact of NRG1 expressions and methylation on multifactorial Hirschsprung disease |
| title_sort | impact of nrg1 expressions and methylation on multifactorial hirschsprung disease |
| topic | Paediatrics |
| url | https://repository.ugm.ac.id/283809/1/238.pdf |
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