title: Plasma matrix metalloproteinase-9 levels, MMP-9 gene haplotypes, and cardiovascular risk in obese subjects.
abstract: Plasma matrix metalloproteinase (MMP)-9 is a predictor of cardiovascular mortality, and MMP-9 polymorphisms affect plasma MMP-9 levels. However, no study examined whether MMP-9 haplotypes affect MMP-9 levels in obese adults. We examined whether MMP-9 polymorphisms and haplotypes are associated with obesity, and whether they affect MMP-9 levels in obese subjects. We examined the plasma levels of MMP-9 and tissue inhibitor of metalloproteinase (TIMP)-1 in 105 subjects with normal weight (controls), 100 obese subjects, and 156 obese subjects with ≥3 metabolic risk factors (MRFs). We determined genotypes for three polymorphisms: C-1562T (rs3918242), Q279R (A>G, rs17576), and R668Q (G>A, rs17577). MMP-9 levels and activity (MMP-9/TIMP-1 ratio) were higher in obese subjects than in controls (P < 0.05). However, MMP-9 levels were higher in obese subjects with ≥3 MRFs than in obese subjects (P < 0.05). Obese subjects with ≥3 MRFs carrying the GA+AA genotypes for R668Q (G>A) polymorphism had higher MMP-9 levels than subjects carrying the AA genotype (P < 0.05). The "T, G, A" haplotype was more common in both groups of obese subjects than in controls (OR 3.95 and 4.39, respectively; P < 0.01). Notably, obese subjects with ≥3 MRFs carrying the "T, G, A" haplotype had higher MMP-9 levels than subjects carrying the "C, A, G" reference haplotype (P < 0.05). The "T, G, A" haplotype was associated with an increased risk of obesity and affected MMP-9 levels in obese subjects with ≥3 MRFs. Our findings suggest that plasma MMP-9 levels and MMP-9 haplotypes may help to discriminate obese subjects at an increased cardiovascular risk.
authors.affiliation: Department of Pharmacology, Institute of Biosciences of Botucatu, Universidade Estadual Paulista (UNESP), Distrito de Rubião Junior S/N, Botucatu, SP, 18618-000, Brazil.
authors.forename: Marcelo R
authors.initials: MR
authors.lastname: Luizon
authors.affiliation: Department of Pharmacology, Ribeirao Preto Medical School, University of São Paulo, Av. Bandeirantes, 3900, Ribeirão Preto, SP, 14049-900, Brazil.
authors.forename: Vanessa A
authors.initials: VA
authors.lastname: Belo
authors.affiliation: Núcleo de Pós-graduação e Pesquisa, Santa Casa de Belo Horizonte, Rua Domingos Vieira, 590, Belo Horizonte, MG, 30150-240, Brazil.
authors.forename: Karla S
authors.initials: KS
authors.lastname: Fernandes
authors.affiliation: Núcleo de Pós-graduação e Pesquisa, Santa Casa de Belo Horizonte, Rua Domingos Vieira, 590, Belo Horizonte, MG, 30150-240, Brazil.
authors.forename: Vanessa L
authors.initials: VL
authors.lastname: Andrade
authors.affiliation: Department of Pharmacology, Ribeirao Preto Medical School, University of São Paulo, Av. Bandeirantes, 3900, Ribeirão Preto, SP, 14049-900, Brazil.
authors.forename: Jose E
authors.initials: JE
authors.lastname: Tanus-Santos
authors.affiliation: Department of Pharmacology, Institute of Biosciences of Botucatu, Universidade Estadual Paulista (UNESP), Distrito de Rubião Junior S/N, Botucatu, SP, 18618-000, Brazil. valsandrim@yahoo.com.br.
authors.forename: Valeria C
authors.initials: VC
authors.lastname: Sandrim
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000097:blood / Q000201:enzymology* / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000097:blood* / Q000235:genetics; D008875:Middle Aged; D009765:Obesity / Q000097:blood / Q000201:enzymology* / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood
chemical_list: D015415:Biomarkers; C560822:TIMP1 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9
keywords: Haplotypes; Matrix metalloproteinase (MMP)-9; Metabolic risk factors; Obesity; Polymorphisms; Tissue inhibitor of matrix metalloproteinase (TIMP)-1