Plasma matrix metalloproteinase-9 levels, MMP-9 gene haplotypes, and cardiovascular risk in obese subjects

• Published in: Molecular biology reports Vol. 43; no. 6; pp. 463 - 471
• Main Authors: Luizon, Marcelo R., Belo, Vanessa A., Fernandes, Karla S., Andrade, Vanessa L., Tanus-Santos, Jose E., Sandrim, Valeria C.
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Netherlands 01.06.2016; Springer Nature B.V
• Subjects: Adult; adults; Animal Anatomy; Animal Biochemistry; Biomarkers - blood; Biomedical and Life Sciences; Cardiovascular Diseases - blood; Cardiovascular Diseases - enzymology; Cardiovascular Diseases - genetics; Female; gelatinase B; Gene Frequency; genes; Genetic Association Studies; Genetic Predisposition to Disease; haplotypes; Histology; Humans; Life Sciences; Linkage Disequilibrium; Male; Matrix; Matrix Metalloproteinase 9 - blood; Matrix Metalloproteinase 9 - genetics; Middle Aged; Morphology; mortality; Obesity; Obesity - blood; Obesity - enzymology; Obesity - genetics; Original Article; Plasma; Polymorphism; Polymorphism, Single Nucleotide; Risk Factors; Tissue Inhibitor of Metalloproteinase-1 - blood; Haplotypes; Obesity; Matrix metalloproteinase (MMP)-9; Metabolic risk factors; Polymorphisms; Tissue inhibitor of matrix metalloproteinase (TIMP)-1
• ISSN: 0301-4851; 1573-4978; 1573-4978
• DOI: 10.1007/s11033-016-3993-z

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.