Haplotype analysis of SERPINE1 gene: Risk for aneurysmal subarachnoid hemorrhage and clinical outcomes
Abstract Background Aneurysmal subarachnoid hemorrhage (aSAH) has high fatality and permanent disability rates due to the severe damage to brain cells and inflammation. The SERPINE1 gene that encodes PAI‐1 for the regulation of tissue plasminogen activator is considered an important therapeutic targ...
| Main Authors: | , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2019-08-01
|
| Series: | Molecular Genetics & Genomic Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/mgg3.737 |
| _version_ | 1828181869979500544 |
|---|---|
| author | Mingkuan Lin Christoph J. Griessenauer Robert M. Starke R. Shane Tubbs Mohammadali M. Shoja Paul M. Foreman Nilesh A. Vyas Beverly C. Walters Mark R. Harrigan Philipp Hendrix Winfield S. Fisher Jean‐Francois Pittet Mali Mathru Robert H. Lipsky |
| author_facet | Mingkuan Lin Christoph J. Griessenauer Robert M. Starke R. Shane Tubbs Mohammadali M. Shoja Paul M. Foreman Nilesh A. Vyas Beverly C. Walters Mark R. Harrigan Philipp Hendrix Winfield S. Fisher Jean‐Francois Pittet Mali Mathru Robert H. Lipsky |
| author_sort | Mingkuan Lin |
| collection | DOAJ |
| description | Abstract Background Aneurysmal subarachnoid hemorrhage (aSAH) has high fatality and permanent disability rates due to the severe damage to brain cells and inflammation. The SERPINE1 gene that encodes PAI‐1 for the regulation of tissue plasminogen activator is considered an important therapeutic target for aSAH. Methods Six SNPs in the SERPINE1 gene (in order of rs2227631, rs1799889, rs6092, rs6090, rs2227684, rs7242) were investigated. Blood samples were genotyped with Taqman genotyping assays and pyrosequencing. The experiment‐wide statistically significant threshold for single marker analysis was set at p < 0.01 after evaluation of independent markers. Haplotype analysis was performed in Haplo.stats package with permutation tests. Bonferroni correction for multiple comparison in dominant, additive, and recessive model was applied. Results A total of 146 aSAH patients and 49 control subjects were involved in this study. The rs2227631 G allele is significant (p = 0.01) for aSAH compared to control. In aSAH group, haplotype analysis showed that G5GGGT homozygotes in recessive model were associated with delayed cerebral ischemia (p < 0.01, Odds Ratio = 5.14, 95% CI = 1.45–18.18), clinical vasospasm (p = 0.01, Odds Ratio = 4.58, 95% CI = 1.30–16.13), and longer intensive care unit stay (p = 0.01). By contrast, the G5GGAG carriers were associated with less incidence of cerebral edema (p < 0.01) and higher Glasgow Coma Scale (p < 0.01). The A4GGGT carriers were associated with less incidence of severe hypertension (>140/90) (p < 0.01). Conclusion The results suggested an important regulatory role of the SERPINE1 gene polymorphism in clinical outcomes of aSAH. |
| first_indexed | 2024-04-12T06:09:01Z |
| format | Article |
| id | doaj.art-003d503ce0da44faa2f8ec1c34f0885d |
| institution | Directory Open Access Journal |
| issn | 2324-9269 |
| language | English |
| last_indexed | 2024-04-12T06:09:01Z |
| publishDate | 2019-08-01 |
| publisher | Wiley |
| record_format | Article |
| series | Molecular Genetics & Genomic Medicine |
| spelling | doaj.art-003d503ce0da44faa2f8ec1c34f0885d2022-12-22T03:44:46ZengWileyMolecular Genetics & Genomic Medicine2324-92692019-08-0178n/an/a10.1002/mgg3.737Haplotype analysis of SERPINE1 gene: Risk for aneurysmal subarachnoid hemorrhage and clinical outcomesMingkuan Lin0Christoph J. Griessenauer1Robert M. Starke2R. Shane Tubbs3Mohammadali M. Shoja4Paul M. Foreman5Nilesh A. Vyas6Beverly C. Walters7Mark R. Harrigan8Philipp Hendrix9Winfield S. Fisher10Jean‐Francois Pittet11Mali Mathru12Robert H. Lipsky13Department of Systems Biology George Mason University Fairfax VirginiaDepartment of Neurosurgery Geisinger, Danville PennsylvaniaDepartment of Neurosurgery and Radiology University of Miami Miami FloridaChildren’s of Alabama Birmingham AlabamaChildren’s of Alabama Birmingham AlabamaDepartment of Neurosurgery University of Alabama at Birmingham Alabama AlabamaDepartment of Neuroscience INOVA Health System Fairfax VirginiaDepartment of Neuroscience INOVA Health System Fairfax VirginiaDepartment of Neurosurgery University of Alabama at Birmingham Alabama AlabamaDepartment of Neurosurgery Saarland University Medical Center, Saarland University Homburg GermanyDepartment of Neurosurgery University of Alabama at Birmingham Alabama AlabamaDepartment of Neurosurgery University of Alabama at Birmingham Alabama AlabamaDepartment of Neurosurgery University of Alabama at Birmingham Alabama AlabamaDepartment of Systems Biology George Mason University Fairfax VirginiaAbstract Background Aneurysmal subarachnoid hemorrhage (aSAH) has high fatality and permanent disability rates due to the severe damage to brain cells and inflammation. The SERPINE1 gene that encodes PAI‐1 for the regulation of tissue plasminogen activator is considered an important therapeutic target for aSAH. Methods Six SNPs in the SERPINE1 gene (in order of rs2227631, rs1799889, rs6092, rs6090, rs2227684, rs7242) were investigated. Blood samples were genotyped with Taqman genotyping assays and pyrosequencing. The experiment‐wide statistically significant threshold for single marker analysis was set at p < 0.01 after evaluation of independent markers. Haplotype analysis was performed in Haplo.stats package with permutation tests. Bonferroni correction for multiple comparison in dominant, additive, and recessive model was applied. Results A total of 146 aSAH patients and 49 control subjects were involved in this study. The rs2227631 G allele is significant (p = 0.01) for aSAH compared to control. In aSAH group, haplotype analysis showed that G5GGGT homozygotes in recessive model were associated with delayed cerebral ischemia (p < 0.01, Odds Ratio = 5.14, 95% CI = 1.45–18.18), clinical vasospasm (p = 0.01, Odds Ratio = 4.58, 95% CI = 1.30–16.13), and longer intensive care unit stay (p = 0.01). By contrast, the G5GGAG carriers were associated with less incidence of cerebral edema (p < 0.01) and higher Glasgow Coma Scale (p < 0.01). The A4GGGT carriers were associated with less incidence of severe hypertension (>140/90) (p < 0.01). Conclusion The results suggested an important regulatory role of the SERPINE1 gene polymorphism in clinical outcomes of aSAH.https://doi.org/10.1002/mgg3.737clinical vasospasmDelayed Cerebral IschemiaSERPINE1Subarachnoid Hemorrhagetissue plasminogen activator |
| spellingShingle | Mingkuan Lin Christoph J. Griessenauer Robert M. Starke R. Shane Tubbs Mohammadali M. Shoja Paul M. Foreman Nilesh A. Vyas Beverly C. Walters Mark R. Harrigan Philipp Hendrix Winfield S. Fisher Jean‐Francois Pittet Mali Mathru Robert H. Lipsky Haplotype analysis of SERPINE1 gene: Risk for aneurysmal subarachnoid hemorrhage and clinical outcomes Molecular Genetics & Genomic Medicine clinical vasospasm Delayed Cerebral Ischemia SERPINE1 Subarachnoid Hemorrhage tissue plasminogen activator |
| title | Haplotype analysis of SERPINE1 gene: Risk for aneurysmal subarachnoid hemorrhage and clinical outcomes |
| title_full | Haplotype analysis of SERPINE1 gene: Risk for aneurysmal subarachnoid hemorrhage and clinical outcomes |
| title_fullStr | Haplotype analysis of SERPINE1 gene: Risk for aneurysmal subarachnoid hemorrhage and clinical outcomes |
| title_full_unstemmed | Haplotype analysis of SERPINE1 gene: Risk for aneurysmal subarachnoid hemorrhage and clinical outcomes |
| title_short | Haplotype analysis of SERPINE1 gene: Risk for aneurysmal subarachnoid hemorrhage and clinical outcomes |
| title_sort | haplotype analysis of serpine1 gene risk for aneurysmal subarachnoid hemorrhage and clinical outcomes |
| topic | clinical vasospasm Delayed Cerebral Ischemia SERPINE1 Subarachnoid Hemorrhage tissue plasminogen activator |
| url | https://doi.org/10.1002/mgg3.737 |
| work_keys_str_mv | AT mingkuanlin haplotypeanalysisofserpine1generiskforaneurysmalsubarachnoidhemorrhageandclinicaloutcomes AT christophjgriessenauer haplotypeanalysisofserpine1generiskforaneurysmalsubarachnoidhemorrhageandclinicaloutcomes AT robertmstarke haplotypeanalysisofserpine1generiskforaneurysmalsubarachnoidhemorrhageandclinicaloutcomes AT rshanetubbs haplotypeanalysisofserpine1generiskforaneurysmalsubarachnoidhemorrhageandclinicaloutcomes AT mohammadalimshoja haplotypeanalysisofserpine1generiskforaneurysmalsubarachnoidhemorrhageandclinicaloutcomes AT paulmforeman haplotypeanalysisofserpine1generiskforaneurysmalsubarachnoidhemorrhageandclinicaloutcomes AT nileshavyas haplotypeanalysisofserpine1generiskforaneurysmalsubarachnoidhemorrhageandclinicaloutcomes AT beverlycwalters haplotypeanalysisofserpine1generiskforaneurysmalsubarachnoidhemorrhageandclinicaloutcomes AT markrharrigan haplotypeanalysisofserpine1generiskforaneurysmalsubarachnoidhemorrhageandclinicaloutcomes AT philipphendrix haplotypeanalysisofserpine1generiskforaneurysmalsubarachnoidhemorrhageandclinicaloutcomes AT winfieldsfisher haplotypeanalysisofserpine1generiskforaneurysmalsubarachnoidhemorrhageandclinicaloutcomes AT jeanfrancoispittet haplotypeanalysisofserpine1generiskforaneurysmalsubarachnoidhemorrhageandclinicaloutcomes AT malimathru haplotypeanalysisofserpine1generiskforaneurysmalsubarachnoidhemorrhageandclinicaloutcomes AT roberthlipsky haplotypeanalysisofserpine1generiskforaneurysmalsubarachnoidhemorrhageandclinicaloutcomes |