TIMP-2 gene polymorphism is associated with intracerebral hemorrhage
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 imp...
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| Main Authors: | , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
October 16, 2009
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| In: |
Cerebrovascular diseases
Year: 2009, Volume: 28, Issue: 6, Pages: 558-563 |
| ISSN: | 1421-9786 |
| DOI: | 10.1159/000247599 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1159/000247599
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| Author Notes: | Bjoern Reuter, Peter Bugert, Mark Stroick, Simone Bukow, Martin Griebe, Michael G. Hennerici, Marc Fatar |
| Summary: | 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. |
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| Item Description: | Gesehen am 22.04.2022 |
| Physical Description: | Online Resource |
| ISSN: | 1421-9786 |
| DOI: | 10.1159/000247599 |