Intracranial aneurysm’s association with genetic variants, transcription abnormality, and methylation changes in ADAMTS genes
Purpose The development of intracranial aneurysm (IA) has been linked to genetic factors. The current study examines the potential role of genes encoding disintegrin and metalloproteinase using thrombospondin motifs (ADAMTS) in IA development. Material and Methods High-throughput whole-genome and wh...
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PeerJ Inc.
2020-02-01
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| Online Access: | https://peerj.com/articles/8596.pdf |
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| author | Shi Chen Mengqi Li Wenqiang Xin Shengze Liu Linfei Zheng Yan Li Mengyao Li Mengxiong Zhan Xinyu Yang |
| author_facet | Shi Chen Mengqi Li Wenqiang Xin Shengze Liu Linfei Zheng Yan Li Mengyao Li Mengxiong Zhan Xinyu Yang |
| author_sort | Shi Chen |
| collection | DOAJ |
| description | Purpose The development of intracranial aneurysm (IA) has been linked to genetic factors. The current study examines the potential role of genes encoding disintegrin and metalloproteinase using thrombospondin motifs (ADAMTS) in IA development. Material and Methods High-throughput whole-genome and whole-exome sequencing were used when screening for deleterious single-nucleotide variants (SNVs) in ADAMTS genes using samples from 20 Han Chinese patients: 19 with familial IA and one patient with sporadic IA. The variant frequencies in these subjects were compared to those in control individuals found in the Genome Aggregation Database. Transcriptome sequencing and methylation sequencing data were retrieved from the Gene Expression Omnibus (GEO) database to identify differentially expressed ADAMTS genes and their methylation sites. We predicted the network of interactions among proteins encoded by the overlapping set of ADAMTS genes showing deleterious variants and both differential expression and abnormal methylation in IA. Possible candidate proteins linked to IA were validated using Western blot analysis. The associations between IA and SNVs rs11750568 in ADAMTS2, as well as rs2301612 and rs2285489 in ADAMTS13, were verified using the Sequenom MassArray system on a separate sample set of 595 Han Chinese patients with sporadic IA and 600 control individuals. Results A total of 16 deleterious variants in 13 ADAMTS genes were identified in our patients, and seven of these genes overlapped with the genes found to be differentially expressed and differentially methylated in the GEO database. Protein–protein interaction analysis predicted that ADAMTSL1 was at the center of the seven genes. ADAMTSL1 protein was lower expressed in IA tissue than in the control cerebral artery. Frequencies of the IA-related SNVs rs11750568 in ADAMTS2 and rs2301612 and rs2285489 in ADAMTS13 were not significantly different between sporadic IA patients and controls. Conclusion IA is associated with genetic variants, differential expression, and abnormal methylation in ADAMTS genes, ADAMTSL1 in particular. |
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| spelling | doaj.art-2c241eb2ca0b43209235e950cbb801762023-12-03T09:55:33ZengPeerJ Inc.PeerJ2167-83592020-02-018e859610.7717/peerj.8596Intracranial aneurysm’s association with genetic variants, transcription abnormality, and methylation changes in ADAMTS genesShi Chen0Mengqi Li1Wenqiang Xin2Shengze Liu3Linfei Zheng4Yan Li5Mengyao Li6Mengxiong Zhan7Xinyu Yang8Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, ChinaDepartment of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, ChinaDepartment of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, ChinaDepartment of Neurosurgery, Fuzhou Second Hospital Affiliated to Xiamen University, Fuzhou, Fujian, ChinaDepartment of Neurosurgery, Fuzhou Second Hospital Affiliated to Xiamen University, Fuzhou, Fujian, ChinaDepartment of Radiology, Zhenning People’s Hospital, Zhengning, Gansu, ChinaDepartment of Neurology, Wuzhong People’s Hospital, Wuzhong, Ningxia, ChinaDepartment of Neurosurgery, Fuzhou Second Hospital Affiliated to Xiamen University, Fuzhou, Fujian, ChinaDepartment of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, ChinaPurpose The development of intracranial aneurysm (IA) has been linked to genetic factors. The current study examines the potential role of genes encoding disintegrin and metalloproteinase using thrombospondin motifs (ADAMTS) in IA development. Material and Methods High-throughput whole-genome and whole-exome sequencing were used when screening for deleterious single-nucleotide variants (SNVs) in ADAMTS genes using samples from 20 Han Chinese patients: 19 with familial IA and one patient with sporadic IA. The variant frequencies in these subjects were compared to those in control individuals found in the Genome Aggregation Database. Transcriptome sequencing and methylation sequencing data were retrieved from the Gene Expression Omnibus (GEO) database to identify differentially expressed ADAMTS genes and their methylation sites. We predicted the network of interactions among proteins encoded by the overlapping set of ADAMTS genes showing deleterious variants and both differential expression and abnormal methylation in IA. Possible candidate proteins linked to IA were validated using Western blot analysis. The associations between IA and SNVs rs11750568 in ADAMTS2, as well as rs2301612 and rs2285489 in ADAMTS13, were verified using the Sequenom MassArray system on a separate sample set of 595 Han Chinese patients with sporadic IA and 600 control individuals. Results A total of 16 deleterious variants in 13 ADAMTS genes were identified in our patients, and seven of these genes overlapped with the genes found to be differentially expressed and differentially methylated in the GEO database. Protein–protein interaction analysis predicted that ADAMTSL1 was at the center of the seven genes. ADAMTSL1 protein was lower expressed in IA tissue than in the control cerebral artery. Frequencies of the IA-related SNVs rs11750568 in ADAMTS2 and rs2301612 and rs2285489 in ADAMTS13 were not significantly different between sporadic IA patients and controls. Conclusion IA is associated with genetic variants, differential expression, and abnormal methylation in ADAMTS genes, ADAMTSL1 in particular.https://peerj.com/articles/8596.pdfADMTSL1BioinformaticsHemorrhagic strokeSingle-nucleotide variants |
| spellingShingle | Shi Chen Mengqi Li Wenqiang Xin Shengze Liu Linfei Zheng Yan Li Mengyao Li Mengxiong Zhan Xinyu Yang Intracranial aneurysm’s association with genetic variants, transcription abnormality, and methylation changes in ADAMTS genes PeerJ ADMTSL1 Bioinformatics Hemorrhagic stroke Single-nucleotide variants |
| title | Intracranial aneurysm’s association with genetic variants, transcription abnormality, and methylation changes in ADAMTS genes |
| title_full | Intracranial aneurysm’s association with genetic variants, transcription abnormality, and methylation changes in ADAMTS genes |
| title_fullStr | Intracranial aneurysm’s association with genetic variants, transcription abnormality, and methylation changes in ADAMTS genes |
| title_full_unstemmed | Intracranial aneurysm’s association with genetic variants, transcription abnormality, and methylation changes in ADAMTS genes |
| title_short | Intracranial aneurysm’s association with genetic variants, transcription abnormality, and methylation changes in ADAMTS genes |
| title_sort | intracranial aneurysm s association with genetic variants transcription abnormality and methylation changes in adamts genes |
| topic | ADMTSL1 Bioinformatics Hemorrhagic stroke Single-nucleotide variants |
| url | https://peerj.com/articles/8596.pdf |
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