A common matrix metalloproteinase (MMP)-2 polymorphism affects plasma MMP-2 levels in subjects environmentally exposed to mercury.
Sci Total Environ
; 409(20): 4242-6, 2011 Sep 15.
Article
em En
| MEDLINE
| ID: mdl-21794897
ABSTRACT
Mercury (Hg) exposure is associated with disease conditions, including cardiovascular problems. Although the mechanisms implicated in these complications have not been precisely defined yet, matrix metalloproteinases (MMPs) may be involved. The gene encoding MMP-2 presents genetic polymorphisms which affect the expression and activity level of this enzyme. A common polymorphism of MMP-2 gene is the C(-1306)T (rs 243865), which is known to disrupt a Sp1-type promoter site (CCACC box), thus leading to lower promoter activity associated with the T allele. This study aimed at examining how this polymorphism affects the circulating MMP-2 levels and its endogenous inhibitor, the tissue inhibitor of metalloproteinase-2 (TIMP-2) in 210 subjects environmentally exposed to Hg. Total blood and plasma Hg concentrations were determined by inductively coupled plasma-mass spectrometry (ICP-MS). MMP-2 and TIMP-2 concentrations were measured in plasma samples by gelatin zymography and ELISA, respectively. Genotypes for the C(-1306)T polymorphism were determined by Taqman® Allele Discrimination assay. We found a positive association (p=0.0057) between plasma Hg concentrations and MMP-2/TIMP-2 (an index of net MMP-2 activity). The C(-1306)T polymorphism modified MMP-2 concentrations (p=0.0465) and MMP-2/TIMP-2 ratio (p=0.0060) in subjects exposed to Hg, with higher MMP-2 levels been found in subjects carrying the C allele. These findings suggest a significant interaction between the C(-1306)T polymorphism and Hg exposure, possibly increasing the risk of developing diseases in subjects with the C allele.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Polimorfismo Genético
/
Metaloproteinase 2 da Matriz
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Exposição Ambiental
/
Poluentes Ambientais
/
Mercúrio
Tipo de estudo:
Etiology_studies
/
Risk_factors_studies
Limite:
Adolescent
/
Adult
/
Aged
/
Aged80
/
Female
/
Humans
/
Male
/
Middle aged
País/Região como assunto:
America do sul
/
Brasil
Idioma:
En
Revista:
Sci Total Environ
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Brasil