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Haplotype Analysis of SERPINE1 Gene: Risk for Aneurysmal Subarachnoid Hemorrhage and Clinical Outcomes

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dc.contributor.author Lin, Mingkuan
dc.contributor.author Griessenauer, Christoph J.
dc.contributor.author Starke, Robert M.
dc.contributor.author Tubbs, R. Shane
dc.contributor.author Shoja, Mohammadali M.
dc.contributor.author Foreman, Paul M.
dc.contributor.author Vyas, Nilesh A.
dc.contributor.author Walters, Beverly C.
dc.contributor.author Harrigan, Mark R.
dc.contributor.author Hendrix, Philipp
dc.contributor.author Fisher, Winfield S.
dc.contributor.author Pittet, Jean-Francois
dc.contributor.author Mathru, Mali
dc.contributor.author Lipsky, Robert H.
dc.date.accessioned 2019-08-20T22:17:03Z
dc.date.available 2019-08-20T22:17:03Z
dc.date.issued 2019
dc.identifier.uri http://hdl.handle.net/1920/11568
dc.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 geno-typed 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 SERPINE1gene polymorphism in clinical outcomes of aSAH. en_US
dc.language.iso en_US en_US
dc.publisher Molecular Genetics & Genomic Medicine en_US
dc.rights Attribution 3.0 United States *
dc.rights.uri http://creativecommons.org/licenses/by/3.0/us/ *
dc.title Haplotype Analysis of SERPINE1 Gene: Risk for Aneurysmal Subarachnoid Hemorrhage and Clinical Outcomes en_US
dc.type Article en_US
dc.identifier.doi 10.1002/mgg3.737


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