A functional matrix metalloproteinase (MMP)-9 polymorphism modifies plasma MMP-9 levels in subjects environmentally exposed to mercury

• Published in: The Science of the total environment Vol. 408; no. 19; pp. 4085 - 4092
• Main Authors: Jacob-Ferreira, Anna L.B., Passos, Carlos J.S., Gerlach, Raquel F., Barbosa, Fernando, Tanus-Santos, Jose E.
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier B.V 01.09.2010; [Amsterdam; New York]: Elsevier Science; Elsevier
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; alleles; Biological and medical sciences; blood; blood plasma; cardiovascular diseases; Chemical and industrial products toxicology. Toxic occupational diseases; Circulating; Diseases; ELISA; Environmental Exposure; Environmental Exposure - statistics & numerical data; enzyme-linked immunosorbent assay; Enzymes; Exposure; Female; gelatin; gelatinase A; genetic polymorphism; genetics; genotype; Humans; Inhibitors; Male; Matrix Metalloproteinase 9; Matrix Metalloproteinase 9 - blood; Matrix Metalloproteinase 9 - genetics; Matrix metalloproteinases; Medical sciences; Mercury; Mercury - blood; Metals and various inorganic compounds; Middle Aged; Polymorphism; Polymorphism, Single Nucleotide; promoter regions; risk; spectroscopy; statistics & numerical data; Tissue Inhibitor of Metalloproteinase-1; Tissue Inhibitor of Metalloproteinase-1 - blood; Toxicology; Young Adult; Mercury; Matrix metalloproteinases; Polymorphism; Human; Genetic variability; Enzyme; Metalloendopeptidases; Genotype; Exposure; Gelatinase B; Heavy metal; Peptidases; Gene; Hydrolases; Environment; Public health
• ISSN: 0048-9697; 1879-1026; 1879-1026
• DOI: 10.1016/j.scitotenv.2010.05.036

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 − 1562 T 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 − 1562 T 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 − 1562 T 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.