Functional matrix metalloproteinase (MMP)-9 genetic variants modify the effects of hemodialysis on circulating MMP-9 levels

Marson, Bernardo P.; Lacchini, Riccardo; Belo, Vanessa A.; Mattos, Silvia Gelpi; Costa, Bartira Ercí­lia Pinheiro da; Poli-de-Figueiredo, Carlos Eduardo; Tanus‐Santos, José Eduardo

doi:10.1016/j.cca.2012.08.014

Cited by 11 publications

(11 citation statements)

References 34 publications

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“…However, conflicting results have been reported (Table 6). In line with our findings, most studies have shown that HD treatment reduced or had no effect on MMP-2 and MMP-9 levels [14,19,35,36]. Variable results have also been reported for the effects of HD on TIMP-1 and TIMP-2 levels (Table 6) [17,20,35].…”

Section: Discussionsupporting

confidence: 86%

“…It has been shown that HD treatment increased circulating TIMP-1 level and the results of the current study support this report [36]. However, the contradicting result, i.e., decreased TIMP-1 due to HD process, also have been reported [17,20].…”

Section: Discussionsupporting

confidence: 81%

“…Rysz et al [20] showed significantly decreasing plasma TIMP-1 and no significant change on TIMP-2 level after an HD session. Comparing our data with this previous report, significantly decreased MMP-2 after an HD session is consistent; however, the Up arrow higher levels than healthy controls, equal symbol similar levels compared with healthy controls, down arrow lower levels than healthy controls, NA not available, NI not indicated, Pat/Con number of CKD patients/number of healthy controls increases in MMP-9 and MMP-9/TIMP-1 are controversial results [36]. These differences between our data and the previous reports may be explained by differences in causal diseases, age, genetic factors, type of dialysis membrane, clinical conditions and pharmacological interventions.…”

Section: Discussionsupporting

confidence: 62%

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Decreases in plasma MMP-2/TIMP-2 and MMP-9/TIMP-1 ratios in uremic patients during hemodialysis

Yang

Hsieh

et al. 2015

Clin Exp Nephrol

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Background Matrix metalloproteinases (MMPs) and their endogenous tissue inhibitors (TIMPs) play important roles in the pathophysiology of renal diseases. Imbalanced MMPs/TIMPs are implicated in the vascular alterations of uremic patients on hemodialysis (HD). We have investigated the plasma levels of MMP-2, MMP-9, TIMP-1 and TIMP-2 in uremic patients and the effects of a course of HD on the changes in these factors. Methods There were 382 uremic patients on regular HD treatment and 50 healthy controls enrolled in this study. The plasma MMP-2 and MMP-9 levels were detected by gelatin zymography, and TIMP-1 and TIMP-2 concentrations were determined by ELISA assay. Results Significantly higher plasma MMP-2 and MMP-9 and decreased TIMP-1 in the uremic patients were detected compared with those in the controls. Therefore, there were markedly higher MMP-2/TIMP-2 and MMP-9/TIMP-1 ratios in the uremic patients. In the course of a single HD session, the plasma MMP-2 level was significantly decreased from pre-HD to post-HD. TIMP-1 concentration was significantly increased from pre-HD to post-HD. Although the HD session did not have a significant effect on the levels of plasma MMP-9 and TIMP-2, both plasma MMP-2/TIMP-2 and MMP-9/TIMP-1 ratios were significantly decreased from pre-HD to post-HD levels.Conclusion HD session could decrease MMP-2 and increase TIMP-1 level in the circulation of uremic patients. The physiological significance of reduced MMPs/TIMPs ratio due to a single HD session is required to further validate.Keywords Hemodialysis Á Matrix metalloproteinase Á Tissue inhibitor of matrix metalloproteinase Á Uremic patient

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Section: Discussionsupporting

confidence: 86%

Section: Discussionsupporting

confidence: 81%

Section: Discussionsupporting

confidence: 62%

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Decreases in plasma MMP-2/TIMP-2 and MMP-9/TIMP-1 ratios in uremic patients during hemodialysis

Yang

Hsieh

et al. 2015

Clin Exp Nephrol

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“…These include VEGF +936C/T, –1154A/G, –2578C/A, and –634G/C [18, 19], MMP2 –1306 C/T and –735 C/T, as well as MMP9 –1562 C/T [20, 21]. These potential genetic risk factors were analyzed in relation to known clinical risk factors of IVH.…”

Section: Methodsmentioning

confidence: 99%

Can Functional Polymorphisms in VEGF and MMP Predict Intraventricular Hemorrhage in Extremely Preterm Newborns?

Prasun¹,

Madan²,

Puthuraya³

et al. 2018

Dev Neurosci

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Background: The pathophysiology of intraventricular hemorrhage (IVH) is multifactorial. This study attempts to identify genetic and clinical factors contributing to IVH in newborns with a focus on those born ≤28 weeks of gestation. Methods: This was a prospective study of 382 consecutive newborns admitted to the neonatal intensive care unit. DNA purification was conducted using standard methods. TaqMan SNP assays were conducted for functional polymorphisms in VEGF (RS699947, RS2010963, RS3025039, and RS1570360) and MMP2 (RS243685 and RS2285053) genes. An RFLP assay was done for a polymorphism in MMP9 (RS3918242). Results: The GG genotype in VEGF RS1570360 (p = 0.013) and the CC genotype in VEGF RS699947 (p = 0.036) were associated with a lower incidence of IVH amongst newborns ≤28 weeks of gestation. Chorioamnionitis, Caucasian race, and patent ductus arteriosus were associated with a higher incidence of IVH. A binary logistic regression analysis of clinical and SNP data that was significant from bivariate analysis demonstrated that VEGF RS1570360 was significantly associated with IVH (p = 0.017). Conclusion: This study demonstrated that the GA/AA genotype in VEGF RS1570360 and the AA/AC genotype in VEGF RS699947 were associated with higher incidence rates of IVH in newborns ≤28 weeks of gestation. A future study is warranted to comprehensively examine VEGF polymorphisms in association with IVH.

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“…It is located at position 2q35-q37 and contains 51 exons (14). Matrix metalloproteinases (MMP) are zinc-dependent endopeptidases that degrade matrix and non-matrix proteins (15). MMPs regulate numerous normal and pathological activities (16).…”

Section: Introductionmentioning

confidence: 99%

Association of COL4A3 (rs55703767), MMP-9 (rs17576)and TIMP-1 (rs6609533) gene polymorphisms with susceptibility to type 2 diabetes

et al. 2017

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Abstract. Type 2 diabetes (T2D) is defined by high levels of glucose in the blood. The collagen IV level is associated with conditions of hyperglycemia and insulin resistance. Collagen type IV α3 chain (COL4A3) is a structural protein of the extracellular matrix (ECM). Matrix metallopeptidase 9 (MMP-9) is an enzyme that degrades the extracellular matrix and its activity is moderated by TIMP metallopeptidase inhibitor 1 (TIMP-1). The aim of the current study was to examine the association between genetic polymorphisms of COL4A3 (rs55703767), MMP-9 (rs17576) and TIMP-1 (rs6609533) in patients with T2D. This case-control study was performed on 120 Iranian patients with T2D and 120 healthy individuals. Genotypes were analyzed using the amplification refractory mutation system-polymerase chain reaction technique. The findings demonstrated significant differences between genotypic and allelic distributions of COL4A3 (G/T) and MMP-9 (A/G) polymorphisms as follows: COL4A3 (G/T); TT vs. GG, odds ratio (OR)= 0.235, 95% confidence interval (CI)=0.063-0.0802 (P=0.013) and T vs. G, OR=0.592, 95% CI= 0.371-0.943 (P= 0.026);

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Functional matrix metalloproteinase (MMP)-9 genetic variants modify the effects of hemodialysis on circulating MMP-9 levels

Abstract: ESKD patients with the QQ genotype for the Q279R polymorphism or with the CLQ haplotype are exposed to more severe increases in MMP-9 levels after hemodialysis. Such patients may benefit from the use of MMP inhibitors.

Cited by 11 publications

References 34 publications

Decreases in plasma MMP-2/TIMP-2 and MMP-9/TIMP-1 ratios in uremic patients during hemodialysis

Decreases in plasma MMP-2/TIMP-2 and MMP-9/TIMP-1 ratios in uremic patients during hemodialysis

Can Functional Polymorphisms in <b><i>VEGF</i></b> and <b><i>MMP</i></b> Predict Intraventricular Hemorrhage in Extremely Preterm Newborns?

Association of COL4A3 (rs55703767), MMP-9 (rs17576)and TIMP-1 (rs6609533) gene polymorphisms with susceptibility to type 2 diabetes

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