Dysregulated expression of androgen metabolism genes and genetic analysis in hypospadias
Abstract Background The aberrant expression of genes involved in androgen metabolism and genetic contribution are unclear in hypospadias. Methods We compared gene expression profiles by RNA sequencing from five non‐hypospadiac foreskins, five mild hypospadiac foreskins, and five severe hypospadiac f...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2020-08-01
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| Series: | Molecular Genetics & Genomic Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/mgg3.1346 |
| _version_ | 1797301051776303104 |
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| author | Zhongzhong Chen Xiaoling Lin Yaping Wang Hua Xie Fang Chen |
| author_facet | Zhongzhong Chen Xiaoling Lin Yaping Wang Hua Xie Fang Chen |
| author_sort | Zhongzhong Chen |
| collection | DOAJ |
| description | Abstract Background The aberrant expression of genes involved in androgen metabolism and genetic contribution are unclear in hypospadias. Methods We compared gene expression profiles by RNA sequencing from five non‐hypospadiac foreskins, five mild hypospadiac foreskins, and five severe hypospadiac foreskins. In addition, to identify rare coding variants with large effects on hypospadias risk, we carried out whole exome sequencing in three patients in a hypospadias family. Results The average expression of androgen receptor (AR) and CYP19A1 were significantly decreased in severe hypospadias (p < .01) and mild hypospadias (p < .05), whereas expression of several other androgen metabolism enzymes, including CYP3A4, HSD17B14, HSD3B7, HSD17B7, CYP11A1 were exclusively significantly expressed in severe hypospadias (p < .05). Compound rare damaging mutants of AR gene with HSD3B1 and SLC25A5 genes were identified in the different severe hypospadias. Conclusions In conclusion, our findings demonstrated that dysregulation of AR and CYP19A1 could play a crucial role in the development of hypospadias. Inconsistent AR expression may be caused by the feedback loop of ESR1 signaling or combined genetic effects with other risk genes. This findings complement the possible role of AR triggered mechanism in the development of hypospadias. |
| first_indexed | 2024-03-07T23:15:51Z |
| format | Article |
| id | doaj.art-454ce8f9e7c2429e8c2bc292707390ec |
| institution | Directory Open Access Journal |
| issn | 2324-9269 |
| language | English |
| last_indexed | 2024-03-07T23:15:51Z |
| publishDate | 2020-08-01 |
| publisher | Wiley |
| record_format | Article |
| series | Molecular Genetics & Genomic Medicine |
| spelling | doaj.art-454ce8f9e7c2429e8c2bc292707390ec2024-02-21T11:08:50ZengWileyMolecular Genetics & Genomic Medicine2324-92692020-08-0188n/an/a10.1002/mgg3.1346Dysregulated expression of androgen metabolism genes and genetic analysis in hypospadiasZhongzhong Chen0Xiaoling Lin1Yaping Wang2Hua Xie3Fang Chen4Department of Urology Shanghai Children’s HospitalShanghai Jiao Tong University Shanghai ChinaDepartment of Urology Huashan HospitalFudan University Shanghai ChinaDepartment of Urology Shanghai Children’s HospitalShanghai Jiao Tong University Shanghai ChinaDepartment of Urology Shanghai Children’s HospitalShanghai Jiao Tong University Shanghai ChinaDepartment of Urology Shanghai Children’s HospitalShanghai Jiao Tong University Shanghai ChinaAbstract Background The aberrant expression of genes involved in androgen metabolism and genetic contribution are unclear in hypospadias. Methods We compared gene expression profiles by RNA sequencing from five non‐hypospadiac foreskins, five mild hypospadiac foreskins, and five severe hypospadiac foreskins. In addition, to identify rare coding variants with large effects on hypospadias risk, we carried out whole exome sequencing in three patients in a hypospadias family. Results The average expression of androgen receptor (AR) and CYP19A1 were significantly decreased in severe hypospadias (p < .01) and mild hypospadias (p < .05), whereas expression of several other androgen metabolism enzymes, including CYP3A4, HSD17B14, HSD3B7, HSD17B7, CYP11A1 were exclusively significantly expressed in severe hypospadias (p < .05). Compound rare damaging mutants of AR gene with HSD3B1 and SLC25A5 genes were identified in the different severe hypospadias. Conclusions In conclusion, our findings demonstrated that dysregulation of AR and CYP19A1 could play a crucial role in the development of hypospadias. Inconsistent AR expression may be caused by the feedback loop of ESR1 signaling or combined genetic effects with other risk genes. This findings complement the possible role of AR triggered mechanism in the development of hypospadias.https://doi.org/10.1002/mgg3.1346ARCYP19A1hypospadiasgene expressionwhole exome sequencing |
| spellingShingle | Zhongzhong Chen Xiaoling Lin Yaping Wang Hua Xie Fang Chen Dysregulated expression of androgen metabolism genes and genetic analysis in hypospadias Molecular Genetics & Genomic Medicine AR CYP19A1 hypospadias gene expression whole exome sequencing |
| title | Dysregulated expression of androgen metabolism genes and genetic analysis in hypospadias |
| title_full | Dysregulated expression of androgen metabolism genes and genetic analysis in hypospadias |
| title_fullStr | Dysregulated expression of androgen metabolism genes and genetic analysis in hypospadias |
| title_full_unstemmed | Dysregulated expression of androgen metabolism genes and genetic analysis in hypospadias |
| title_short | Dysregulated expression of androgen metabolism genes and genetic analysis in hypospadias |
| title_sort | dysregulated expression of androgen metabolism genes and genetic analysis in hypospadias |
| topic | AR CYP19A1 hypospadias gene expression whole exome sequencing |
| url | https://doi.org/10.1002/mgg3.1346 |
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