Polimorfismo de la matriz de metaloproteinasa 2-

A Polymorphism in the Matrix Metalloproteinase-2 (MMP-2 -1306T > C)
Gene Promoter is Associated with High Risk of Ischemic Stroke in
Hypertensive Patients
Nélida A. Gonzalez-Hernandez1, Rebeca O. Millan-Guerrero2, Gabriel Ceja-Espiritu1,
Luz M. Baltazar-Rodriguez1, Rafael Rodriguez-Salazar2, Bertha A. Olmedo-Buenrostro3,
Irma G. Enriquez-Maldonado4, Valery Melnikov1, José Guzman-Esquivel1,2
and Ivan Delgado-Enciso1*
1 School of Medicine, Universidad de Colima, Colima, Colima, PC 28040, Mexico
2 Hospital General de Zona Nº 1, Instituto Mexicano del Seguro Social, Colima, Colima, PC 28000, Mexico
3 School of Nursing, Universidad de Colima, Colima, Colima, PC 28040, Mexico
4 Hospital Regional Universitario, Secretaría de Salud del Estado de Colima, Colima, Colima, PC 28040, Mexico
Received September 5, 20088; accepted Novermber 10, 2008
ABSTRACT
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.
Key words: genetics of stroke, hypertension, ischemic stroke, polymorphism, risk factors for stroke.