TIMP-2 gene polymorphism is associated with intracerebral hemorrhage

• Verfasst von: Reuter, Björn [VerfasserIn]
• Verfasst von: Bugert, Peter [VerfasserIn]
• Verfasst von: Stroick, Mark Gregor [VerfasserIn]
• Verfasst von: Bukow, Simone [VerfasserIn]
• Verfasst von: Griebe, Martin [VerfasserIn]
• Verfasst von: Hennerici, Michael G. [VerfasserIn]
• Verfasst von: Fatar, Marc [VerfasserIn]
• Titel: TIMP-2 gene polymorphism is associated with intracerebral hemorrhage
• Verf.angabe: Bjoern Reuter, Peter Bugert, Mark Stroick, Simone Bukow, Martin Griebe, Michael G. Hennerici, Marc Fatar
• E-Jahr: 2009
• Jahr: October 16, 2009
• Umfang: 6 S.
• Fussnoten: Gesehen am 22.04.2022
• Titel Quelle: Enthalten in: Cerebrovascular diseases
• Ort Quelle: Basel : Karger, 1991
• Jahr Quelle: 2009
• Band/Heft Quelle: 28(2009), 6, Seite 558-563
• ISSN Quelle: 1421-9786
• DOI: doi:10.1159/000247599
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Adult
• Sach-SW: Aged
• Sach-SW: Aged, 80 and over
• Sach-SW: Case-Control Studies
• Sach-SW: Cerebral Hemorrhage
• Sach-SW: Female
• Sach-SW: Gene Frequency
• Sach-SW: Genetic Predisposition to Disease
• Sach-SW: Genotype
• Sach-SW: Heterozygote
• Sach-SW: Homozygote
• Sach-SW: Humans
• Sach-SW: Incidence
• Sach-SW: Male
• Sach-SW: Middle Aged
• Sach-SW: Polymorphism, Single Nucleotide
• Sach-SW: Tissue Inhibitor of Metalloproteinase-2
• K10plus-PPN: 1800055641

Abstract

BACKGROUND: Both ischemic stroke and intracerebral hemorrhage are associated with altered expression and activation of matrix metalloproteinases (MMPs). Particularly relevant are MMP-2 and MMP-9. This proteolytic effect is dampened by tissue inhibitors of metalloproteinases (TIMPs). TIMP-2 is an important endogenous inhibitor of MMP-2. Alterations in the TIMP-2 gene expression may contribute to the incidence of ischemic stroke and intracerebral hemorrhage. - METHODS: TIMP-2 gene SNP -261G/A was genotyped from sequentially recruited stroke patients (n = 356, f/m 151/205, mean age 68.2 years, range 19-100 years) and gender and age matched controls (n = 253, f/m 114/139, mean age 68.5 years, range 32-92 years). The SNP -261G/A was detected after gene sequencing of 95 patients and controls. Furthermore, in a subgroup of 93 patients the serum levels of TIMP-2 were measured during the first 7 days after stroke onset and compared to the genotype. - RESULTS: SNP -261G/A in the TIMP-2 gene shows an allele frequency of approximately 39.14%. Homozygosity for allele A is associated significantly with the development of ICH (p = 0.025, OR = 2.020, CI = 1.115-3.661) as compared to heterozygosity and homozygosity for allele G (recessive genotypic model). Concordantly, the serum levels of TIMP-2 showed a nonsignificant decreases, depending on the genotype (p = 0.111). - CONCLUSION: We investigated a SNP 261 base pairs upstream of the start codon in exon 1 of TIMP-2. Our data suggest that carriers of homozygosity for allele A are at increased risk of developing intracerebral hemorrhage.