Article
Genetic variants of matrix metalloproteinases in patients with intracranial aneurysms
Genetische Varianten von Matrix-Metalloproteinasen bei Patienten mit intrakraniellen Aneurysmen
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Published: | April 23, 2004 |
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Outline
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Objective
Remodelling of the extracellular matrix seems to be a crucial event in the pathogenesis of intracranial aneurysms. Matrix-metalloproteinases (MMPs) are the most important degrading enzymes in the extracellular matrix. In particular, the MMP-2 / MMP-14 complex as well as MMP-3 and MMP-7 were found to be overexpressed in aneurysm tissue. We conducted a case-control study to investigate whether genetic variants in their coding genes might be associated with that phenotype.
Methods
The entire coding sequences of MMPs-2, -3, -7, and -14 were analyzed by a direct sequencing approach with primers located in adjacent intronic sequences. The primary study sample consisted of 40 patients with at least one intracranial aneurysm and 40 anonymous controls. Genotypes were determined and checked for being in Hardy-Weinberg equilibrium. Those in disequilibrium were analyzed in a second study sample of another 40 patients and controls, respectively. Differences between the genotype- and allele frequencies of the identified polymorphisms were investigated.
Results
We identified ten, four, and four SNPs in the MMP-2, -3, and -14 genes, respectively, while there were no SNPs in the coding region of the MMP-7 gene. Deviation from Hardy-Weinberg equilibrium was only detected for three SNPs of MMP-2, which could not be confirmed by the analysis of a second study sample. There were no differences in genotype- and allele frequencies of any SNP between patient and control groups.
Conclusions
SNPs within the coding region and adjacent intronic sequences of MMPs known to be involved in extracellular matrix remodelling in the aneurysm wall, are not associated with the phenotype in our Caucasian population.