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KMID : 0381120080300060533
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Genes and Genomics
2008 Volume.30 No. 6 p.533 ~ p.540
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A Polymorphism in the Matrix Metalloproteinase-2 (MMP-2 -1306T > C) Gene Promoter is Associated with High Risk of Ischemic Stroke in Hypertensive Patients
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Gonzalez-Hernandez Nelida A.
Millan-Guerrero Rebeca O.
Baltazar-Rodriguez Luz M.
Rodriguez-Salazar Rafael
Olmedo-Buenrostro Bertha A.
Enriquez-Maldonado Irma G.
Melnikov Valery
Guzman-Esquivel Jose
Delgado-Enciso Ivan
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Abstract
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The action of matrix metalloproteinases (MMPs) can weaken the arterial wall, contributing to the destabilizing and rupture of atheromatous plaque. Within the MMPs, type 2 stands out due to its action on basement membrane constituents. Previous studies have revealed elevated levels of MMP-2 in the acute phase of ischemic stroke (IS). An MMP-2 single nucleotide polymorphism, -1306T > C (rs243865), displayed strikingly high promoter activity with the C allele. Our study analyzed whether or not the MMP-2 -1306T > C polymorphism contributed to the development of IS in a Mexican population. Ninety-eight patients with IS and 213 control subjects were analyzed. Genomic DNA isolation, polymerase chain reaction (PCR), and polymorphism detection by restriction enzyme digestion were performed to detect MMP-2 -1306T > C polymorphism. An increased probability of IS associated with the MMP-2 CC genotype (OR, 1.70; 95% CI, 1.02-2.85) was found. IS risk associated with the CC genotype was more pronounced in hypertensive subjects (OR, 2.81; 95% CI, 1.4-5.5). The CC genotype was not associated with the development of primary hypertension. The data suggest that MMP-2 -1306T > C polymorphism greatly contributes to IS development in the population studied, principally in hypertensive subjects. This case-control study lends support to the association of MMP-2 with stroke at the genetic level, an association consistent with MMP-2 participation in IS physiopathology.
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KEYWORD
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genetics of stroke, hypertension, ischemic stroke, polymorphism, risk factors for stroke
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