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|Title:||A functional matrix metalloproteinase (MMP)-9 polymorphism modifies plasma MMP-9 levels in subjects environmentally exposed to mercury|
|Author:||Jacob-Ferreira, Anna L.B.|
Passos, Carlos J.S.
Gerlach, Raquel F.
Barbosa Jr., Fernando
Tanus-Santos, Jose E.
|Abstract:||Mercury (Hg) exposure causes health problems including cardiovascular diseases. Although precise mechanisms have not been precisely defined yet, matrix metalloproteinases (MMPs) may be involved. The gene encoding MMP-9 presents genetic polymorphisms which affect the expression and activity level of this enzyme. Two polymorphisms in the promoter region [C− 1562T and (CA)n] are functionally relevant, and are implicated in several diseases. This study aimed at examining how these polymorphisms affect the circulating MMP-9 levels and its endogenous inhibitor, the tissue inhibitor of metalloproteinase-1 (TIMP-1) in 266 subjects environmentally exposed to Hg. Blood and plasma Hg concentrations were determined by inductively coupled plasma-mass spectrometry (ICP-MS). MMP-9 and TIMP-1 concentrations were measured in plasma samples by gelatin zymography and ELISA, respectively. Genotypes for the C− 1562T and the microsatellite (CA)n polymorphisms were determined. We found a positive association (P < 0.05) between plasma Hg concentrations and MMP-9/TIMP-1 ratio (an index of net MMP-9 activity). When the subjects were divided into tertiles with basis on their plasma Hg concentrations, we found that the (CA)n polymorphism modified MMP-9 concentrations and MMP-9/TIMP-1 ratio in subjects with the lowest Hg concentrations (first tertile), with the highest MMP-9 levels being found in subjects with genotypes including alleles with 21 or more CA repeats (H alleles) (P < 0.05). Conversely, this polymorphism had no effects on subjects with intermediate or high plasma Hg levels (second and third tertiles, respectively). The C− 1562T polymorphism had no effects on MMP-9 levels. These findings suggest a significant interaction between the (CA)n polymorphism and low levels of Hg exposure, possibly increasing the risk of developing diseases in subjects with H alleles|
Metaloproteinases da matriz
|Appears in Collections:||FCM - Artigos e Outros Documentos|
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