Haplotype analysis of SERPINE1 gene: Risk for aneurysmal subarachnoid hemorrhage and clinical outcomes.
Alleles
Brain Edema
/ epidemiology
Brain Ischemia
/ epidemiology
Case-Control Studies
Genetic Predisposition to Disease
/ genetics
Genotype
Glasgow Coma Scale
Haplotypes
Humans
Hypertension
Incidence
Odds Ratio
Plasminogen Activator Inhibitor 1
/ genetics
Polymorphism, Single Nucleotide
Subarachnoid Hemorrhage
/ epidemiology
Tissue Plasminogen Activator
SERPINE1
Delayed Cerebral Ischemia
Subarachnoid Hemorrhage
clinical vasospasm
tissue plasminogen activator
Journal
Molecular genetics & genomic medicine
ISSN: 2324-9269
Titre abrégé: Mol Genet Genomic Med
Pays: United States
ID NLM: 101603758
Informations de publication
Date de publication:
08 2019
08 2019
Historique:
received:
26
03
2019
accepted:
24
04
2019
pubmed:
4
7
2019
medline:
23
6
2020
entrez:
4
7
2019
Statut:
ppublish
Résumé
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. 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. 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). The results suggested an important regulatory role of the SERPINE1 gene polymorphism in clinical outcomes of aSAH.
Sections du résumé
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.
Identifiants
pubmed: 31268630
doi: 10.1002/mgg3.737
pmc: PMC6687628
doi:
Substances chimiques
Plasminogen Activator Inhibitor 1
0
SERPINE1 protein, human
0
Tissue Plasminogen Activator
EC 3.4.21.68
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e737Informations de copyright
© 2019 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.
Références
Circulation. 2005 Sep 20;112(12):1728-35
pubmed: 16172282
J Cereb Blood Flow Metab. 2012 Sep;32(9):1659-76
pubmed: 22781330
Am J Hum Genet. 2002 Dec;71(6):1386-94
pubmed: 12439824
Cardiovasc Ther. 2010 Oct;28(5):e72-91
pubmed: 20626406
World Neurosurg. 2017 Sep;105:672-677
pubmed: 28599907
Curr Atheroscler Rep. 2017 Oct 23;19(12):50
pubmed: 29063300
Brain. 2008 Oct;131(Pt 10):2662-5
pubmed: 18819992
Br J Anaesth. 2012 Sep;109(3):315-29
pubmed: 22879655
Nat Med. 2003 Oct;9(10):1313-7
pubmed: 12960961
Menopause. 2005 Mar;12(2):136-43
pubmed: 15772559
J Biomech. 2015 Sep 18;48(12):3044-51
pubmed: 26283412
J Am Soc Nephrol. 2008 Mar;19(3):503-14
pubmed: 18199803
Physiol Rev. 2001 Jul;81(3):1065-96
pubmed: 11427692
Am J Hum Genet. 2002 Feb;70(2):425-34
pubmed: 11791212
Neurol Med Chir (Tokyo). 2014 Jun 17;54(6):457-64
pubmed: 24305025
Neurol Res. 2003 Apr;25(3):254-62
pubmed: 12739233
J Neurosci Res. 2002 Jul 1;69(1):1-9
pubmed: 12111810
Eur J Anaesthesiol. 2016 Sep;33(9):662-9
pubmed: 27355865
Hum Mutat. 2010 Nov;31(11):1223-32
pubmed: 20809528
Blood. 2008 May 1;111(9):4496-9
pubmed: 18285546
J Neurosurg. 2016 Dec;125(6):1383-1389
pubmed: 26871202
Gene. 2018 Oct 5;673:167-173
pubmed: 29908999
J Neurosurg. 2005 Jul;103(1):18-24
pubmed: 16121968
Mol Genet Genomic Med. 2019 Aug;7(8):e737
pubmed: 31268630
J Clin Invest. 2004 May;113(10):1447-55
pubmed: 15146242
Curr Neuropharmacol. 2009 Dec;7(4):269-75
pubmed: 20514206
Cold Spring Harb Perspect Biol. 2011 Dec 01;3(12):
pubmed: 21917992
N Engl J Med. 1992 Mar 12;326(11):733-6
pubmed: 1738378
PLoS One. 2011 Mar 22;6(3):e18067
pubmed: 21445367
Cancer Res. 2014 Jan 1;74(1):38-43
pubmed: 24247717
Hum Genet. 2012 May;131(5):747-56
pubmed: 22143225
Neurol Res Int. 2013;2013:291895
pubmed: 23691311
Exp Neurol. 2004 Sep;189(1):25-32
pubmed: 15296833
Proc Natl Acad Sci U S A. 1995 Mar 14;92(6):1851-5
pubmed: 7892190
Asian J Neurosurg. 2017 Jul-Sep;12(3):374-381
pubmed: 28761511
Front Cell Neurosci. 2016 Mar 04;10:56
pubmed: 26973468
J Neurointerv Surg. 2015 Nov;7(11):855-60
pubmed: 25200246
Angiology. 1973 Nov;24(10):627-34
pubmed: 4761033
Arterioscler Thromb Vasc Biol. 2007 Oct;27(10):2250-7
pubmed: 17656673
J Neurosci. 1996 Apr 1;16(7):2220-5
pubmed: 8601802
Nucleic Acids Res. 2014 Jul;42(Web Server issue):W361-7
pubmed: 24829458
J Neurosurg. 2017 May;126(5):1530-1536
pubmed: 27177181
Arch Neurol. 2011 Jan;68(1):31-6
pubmed: 20837823
Br J Anaesth. 2007 Jul;99(1):102-18
pubmed: 17525049
Am J Hum Genet. 2000 Oct;67(4):947-59
pubmed: 10954684
Nat Rev Mol Cell Biol. 2018 May;19(5):327-341
pubmed: 29339797
Blood. 2012 Dec 6;120(24):4873-81
pubmed: 22990020
J Neurol Neurosurg Psychiatry. 2014 Dec;85(12):1343-53
pubmed: 24847164
Stroke. 2005 Sep;36(9):1954-9
pubmed: 16051896