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.

Lipid Peroxidation, Protein Oxidation, Gelatinases, and Their Inhibitors in a Group of Adults with Obesity

“…Data about MMPs in obese subjects have often shown an increase of their plasma levels and a variable behavior of their inhibitors. Adult obese subjects showed an increase of MMP-9 [9,[33][34][35] and MMP-9/ TIMP-1 ratio [9,35]. Contrasting were the data about MMP-2, increased in a group of 163 obese subjects [34] and in patients with MS, mostly overweight or obese [36,37], but decreased in a group of premenopausal obese women [33].…”

The Involvement of Genes of Matrix Metalloproteinases in the Development of Arteial Hypertension and Its Complication (Review)

“…Спектр генов-кандидатов, потенциально вовлеченных в формирование АГ и ее осложнений, постоянно расширяется, на данный момент их известно более 150 [3,6,30]. Согласно исследованиям последних лет, несомненный вклад в формирование артериальной гипертензии вносят гены матриксных металлопротеиназ (ММР) [38,40,41]. Это группа ферментов с широким спектром биологических функций, которые отвечают за гидролиз всех компонентов внеклеточного матрикса и участвуют во всех патологических событиях сердечнососудистого континуума [10,12,14,22 Нет ассоциации -1612 5A/6A ММP-3 rs3025058 с развитием артериальной гипертонии [9] Аллель -799 Т полиморфизма rs11225395 ММP-8 ассоциирован с артериальной гипертензией и аневризмой аорты [7] Полиморфизм -1562C/Т ММP-9 ассоциирован с развитием артериальной гипертензии [18] Полиморфизм -1562 C/T ММP-9 ассоциирован с возникновением инсульта [8] Заключение.…”

Cubilin Single Nucleotide Polymorphism Variants are Associated with Macroangiopathy While a Matrix Metalloproteinase-9 Single Nucleotide Polymorphism Flip-Flop may Indicate Susceptibility of Diabetic Nephropathy in Type-2 Diabetic Patients

“…Therefore, the present study is based on this more up-to-date definition and in line with currently listed frequencies. Both definitions, however, were used in the scientific field and for a multitude of studies and disease [27,28]. Remarkably, in some of these studies, the minor allele frequency for the A-or the G-allele (based on the used definition Gln279Arg or Arg279Gln) had nearly the same frequency in controls, indicating a misinterpretation of wild-typeand nonwild-type alleles.…”