title: A common matrix metalloproteinase (MMP)-2 polymorphism affects plasma MMP-2 levels in subjects environmentally exposed to mercury.
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.
authors.affiliation: Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas, Campinas, Brazil.
authors.forename: Anna L B
authors.initials: AL
authors.lastname: Jacob-Ferreira
authors.forename: Riccardo
authors.initials: R
authors.lastname: Lacchini
authors.forename: Raquel F
authors.initials: RF
authors.lastname: Gerlach
authors.forename: Carlos J S
authors.initials: CJ
authors.lastname: Passos
authors.forename: Fernando
authors.initials: F
authors.lastname: Barbosa
authors.forename: Jose E
authors.initials: JE
authors.lastname: Tanus-Santos
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001938:Brazil; D002318:Cardiovascular Diseases / Q000097:blood / Q000139:chemically induced / Q000235:genetics; D004781:Environmental Exposure / Q000032:analysis*; D004785:Environmental Pollutants / Q000097:blood / Q000633:toxicity*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000097:blood* / Q000235:genetics*; D008628:Mercury / Q000097:blood / Q000633:toxicity*; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012306:Risk; D011795:Surveys and Questionnaires; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000097:blood; D055815:Young Adult
chemical_list: D004785:Environmental Pollutants; C560823:TIMP2 protein, human; D019716:Tissue Inhibitor of Metalloproteinase-2; D020778:Matrix Metalloproteinase 2; D008628:Mercury