TIMP-2 gene polymorphism is associated with intracerebral hemorrhage
Autor: | Mark Stroick, Michael G. Hennerici, Marc Fatar, Peter Bugert, Simone Bukow, Bjoern Reuter, Martin Griebe |
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Rok vydání: | 2009 |
Předmět: |
Adult
Male Pathology medicine.medical_specialty Heterozygote Genotype Single-nucleotide polymorphism Matrix metalloproteinase Polymorphism Single Nucleotide Gene Frequency Medicine SNP Humans Genetic Predisposition to Disease Stroke Aged Cerebral Hemorrhage Intracerebral hemorrhage Aged 80 and over Tissue Inhibitor of Metalloproteinase-2 business.industry Incidence Homozygote Middle Aged medicine.disease Neurology Case-Control Studies Ischemic stroke Female Neurology (clinical) Gene polymorphism Cardiology and Cardiovascular Medicine business |
Zdroj: | Cerebrovascular diseases (Basel, Switzerland). 28(6) |
ISSN: | 1421-9786 |
Popis: | 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. |
Databáze: | OpenAIRE |
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