MMP-9 C-1562T Polymorphism Research Articles

Meta-analysis of matrix metalloproteinase (MMP)-9 C1562T polymorphism and susceptibility to ischemic stroke in the Chinese population.

ObjectiveMany studies have shown that the C1562T polymorphism in the matrix metalloproteinase (MMP)-9 gene promoter is associated with susceptibility to ischemic stroke (IS), but the association between them remains controversial. Our objective was to explore the relationship between MMP9 C1562T polymorphism and susceptibility to IS in the Chinese population.MethodsWe conducted a database search of Wanfang, China Science and Technology Journal database, China National Knowledge Infrastructure, Medline, Embase, PubMed and Springerlink through September 2019. Meta-analysis was performed using Stata15.0 software (StataCorp LP, College Station, TX, USA).ResultsThirteen articles were included, including 3,996 patients and 3,815 controls. Among the Chinese population, the results showed no significant difference for the allele model (T vs. C; odds ratio = 1.05, 95%CI: 0.80–1.37). Significant differences were found in the dominant model (TT+TC vs. CC; odds ratio = 2.94, 95%CI: 1.58–5.45) and in the recessive model (TT vs. TC+CC; pooled OR = 0.81, 95%CI: 0.66–0.99). Neither the homozygous model or heterozygous model was significant.ConclusionWe identified a correlation between MMP-9 C1562T polymorphism and IS in the Chinese population; the TT+TC genotype may increase the risk of IS.

Brain Abscess Risk Associated with Genotypic Polymorphism of the Matrix Metalloproteinase-1, -2, -3, and -9 in North Indian Population

BackgroundBrain abscess develops in response to a parenchymal infection due to pyogenic bacteria. MMPs (matrix metalloproteinases) play vital role in many infectious and central nervous system (CNS) diseases. The present study evaluated the association of specific alleles/ genotypes of MMP-1, -2, -3, and -9 with brain abscess.MethodsA total of 100 brain abscess patients and 100 healthy controls were included in the study. Predisposing factors were identified in 70 brain abscess patients. Out of 100 brain abscess samples, 66 were culture positive. MMP-1-1607 1G/2G, MMP-2- C-1306-T, MMP-3 -1171 5A/6A, and MMP-9 C-1562Tgenotypes were detected by PCR-RFLP. Levels of these MMPs were determined in patients’ sera by ELISA and correlated with different genotypes.ResultsThe genotypic distributions of MMP-1-1607 1G/2G, MMP-2- C-1306-T, MMP-3 -1171 5A/6A, and MMP-9 C-1562T were significantly different between patients and controls. Homozygous genotype of MMP-1, -3, and -9 (P < 0.001, P = 0.04, and P = 0.03, respectively) and heterozygous genotype of MMP-2 (P < 0.001) showed significant association with brain abscess. Individuals with mutant genotypes had elevated levels of these MMPs. Furthermore, heterozygous (5A/6A and C/T, respectively) genotypes of MMP-3 and -9 also showed significant association with brain abscess patients having predisposing factors. When comparison was made between culture positive and culture negative results, of MMP-1 2G/2G and MMP-9 T/T, C/T genotype showed significant association with culture positive patientsConclusionPolymorphism of MMP-1-1607 1G/2G, MMP-2- C-1306-T, MMP-3 -1171 5A/6A, and MMP-9 C-1562T polymorphisms lead to increased production of these molecules, which appear to be a risk for the development of brain abscess in North Indian population.Disclosures All authors: No reported disclosures.

Matrix metalloproteinase-9 and MMP-2 functional promoter polymorphisms and end-stage renal disease in dialysis patients: Correlation with oxidative stress marker

Background: End-stage renal disease (ESRD) is a chronic clinical condition that starts with an initial damage and ultimately develops into a complete loss of kidney function with an unknown mechanism. MMP-9C1562T (rs243866) and MMP-2G1575A (rs3918242) polymorphisms in the promoter region are associated with the incidence of many diseases including cardiovascular, hypertension, chronic kidney disease (CKD), and diabetes mellitus which result in ESRD. Objective: This study was conducted to investigate the possible effect of MMP-9C1562T and MMP-2G1575A polymorphisms on the incidence of ESRD in Kermanshah population as well as their correlation with the serum level of malondialdehyde (MDA). Materials and Methods: The present study was conducted through a case-control method. A total of 136 unrelated ESRD patients and 137 unrelated healthy individuals as the control group matched with patients based on the age and sex. MMP-9C1562T and MMP-2G1575Apolymorphisms were determined using the PCR-RFLP method and serum levels of MDA by High performance liquid chromatography. Results: We found that the frequency of MMP-9C1562T and MMP-2G1575A functional promoter genotypes and alleles in ESRD patients was significantly different compared to the control group. MMP-9C1562T and MMP-2G1575A alleles act synergistically to increase the risk of ESRD by 1.41 times (P = 0.008). In addition, results of this study demonstrated that there is a significant increase in the serum level of MDA in the presence of a dominant model of MMP-9 genotypes (T/T+ C/T vs C/C) and MMP-2 genotypes (A/A+G/A vs G/G) in ESRD patients compared to controls also increased the risk of ESRD 1.36 and 1.4 folds, respectively. Conclusion: We found in this study that MMP-9C1562T and MMP-2G1575A alleles synergistically increase the risk of ESRD but also raise the serum level of MDA in ESRD patients. This information may be important in the evaluation of ESRD progression and in the elucidation of the mechanisms of the disease pathogenesis. Further studies with larger sample sizes and different ethnicities are necessary to confirm these findings.

Association of MMP-9 C-1562T polymorphism with risk of Henoch-Schönlein purpura nephritis in children of southeast China

Henoch-Schonlein purpura nephritis (HSPN) is the most prevalent vasculitis in childhood worldwide. Although the etiology of HSPN is not yet fully elucidated, it is believed to be closely related with infections and genetic predispositions. In this study, a cohort of children from southeast China, including 108 healthy controls and 184 patients were involved in. We scanned the promoter region and the whole gene for genetic variations. A C/T transition located in the promoter region of MMP-9 gene, C-1562T was identified. Subjects were genotyped by using SNaPshot sequencing and the frequencies of CC, CT and TT genotypes were 43, 33 and 24% in patients and 53, 37 and 10% in healthy controls. Allele distribution was found to be in Hardy–Weinberg equilibrium (P = 0.17). Association analysis revealed that the polymorphism was significantly related with HSPN risk (P < 0.05) and T allele was shown to be a risk factor (P = 0.003, odds ratio (OR) 1.63, 95% confidence interval (CI) 1.13–2.34). Additionally, we measured the serum MMP-9 concentration and quantified the mRNA expression. Results showed that an elevated protein level was observed in patients compared with controls in both ELISA (P = 0.0029, 136.5 μg/L vs. 103.9 μg/L) and Western blot assays. Furthermore, we also detected 1.93-fold increase in the mRNA transcription in patients carrying homozygous TT genotype, indicating enhanced promoter activity caused by the polymorphism. Based on the incidence risk, a cut-off value of serum MMP-9 served as HSPN diagnosis was suggested at 155 μg/L. Conclusively, our findings suggested that MMP-9 polymorphism was significantly associated with HSPN susceptibility, and C-1562T T allele contributed to HSPN development.

Matrix metalloproteinase-7 A-181G and its interaction with matrix metalloproteinase-9 C-1562T polymorphism in preeclamptic patients: association with malondialdehyde level and severe preeclampsia.

The abnormal activation of matrix metalloproteinases (MMPs) during pregnancy might be involved in the pathogenesis of preeclampsia. The aim of present study was to investigate the possible influence of MMP-7 A-181G and its interaction with MMP-9 C- 1562T polymorphism on the risk of preeclampsia and lipid peroxidation level. In a case-control study the MMP-7 A-181G and MMP-9 C-1562T polymorphisms were studied in 168 preeclamptic and 154 healthy pregnant women from Western Iran. The MMP-7 and-9 genotypes were detected using polymerase chain reaction-restriction fragment length polymorphism method. The frequency of MMP-7 G allele in mild- (37.4 %) and severe-preeclampsia (45.6 %) and controls (40.3 %) were not significantly different. In preeclamptic patients in the presence of MMP-7 AG + GG genotype there was a significantly higher concentration of malondialdehyde (MDA) (10.52 ± 4.18 μM, p = 0.017) compared to that in AA genotype carriers (9 ± 2.89 μM). Also, in the presence of both MMP-7 G and MMP-9 T alleles the MDA concentration (11.6 ± 4.9 μM) was significantly higher compared to the concomitant presence of MMP-7 A and MMP-9 C wild alleles (9.2 ± 3.1 μM, p = 0.02). There was an interaction between two alleles of MMP-7 G and MMP-9 T that significantly increased the risk of severe preeclampsia by 1.4-fold (OR = 1.4, 95 % CI = 1.06-1.85, p = 0.016). The present study indicates lack of a direct influence of MMP-7 A-181G polymorphism on the risk of preeclampsia. However, this polymorphism through elevation of MDA level as a marker of lipid peroxidation and interaction with MMP-9 C-1562T polymorphism might be associated with the risk of severe preeclampsia.

The Association of MMP-9 Enzyme Activity, MMP-9 C1562T Polymorphism, and MMP-2 and -9 and TIMP-1, -2, -3, and -4 Gene Expression in Lung Cancer

To investigate the association of gene expression of MMP-2 and -9, and TIMP-1, -2, -3, and -4 and polymorphism frequencies of MMP-9 C1562T and plasma MMP-9 enzyme activity in lung cancer patients. In this study, DNA and RNA samples were extracted from peripheral blood of 300 subjects (200 lung cancer patients and 100 controls). MMP-9 C1562T polymorphism was determined using restriction fragment length polymorphism (RFLP) method, and expression of MMP-2 and -9, TIMP-1, -2, -3, and -4 was determined using reverse transcriptase polymerase chain reaction. Plasma MMP-9 enzyme activity levels were measured using enzyme-linked immunosorbent assay. The frequencies of C1562T genotypes were found to be CC 67%, CT 30%, and TT 3% in the control group and CC 75%, CT 24%, and TT 1% in the patient group. It was determined that CC genotype frequency increases significantly in patients according to control group. Plasma MMP-9 enzyme activity levels increased in patients with lung cancer compared to the control group. The cut-off value of MMP-9 enzyme activity was determined as 7.76 ng/mL by receiver operating characteristics curve analysis. The sensitivity, specificity, positive predictive value, and negative predictive value were 77%, 51%, 75.9%, and 52.6%, respectively. The expression of MMP-2 and TIMP-1 was found to be higher in lung cancer patients. Finally, we claim that determination of MMP-9 enzyme levels and expression of MMP-2 and -9 and TIMP-1 can be used as a marker in lung cancer.

MMP2 promoter polymorphism (C‐1306T) and risk of recurrence in patients with hepatocellular carcinoma after transplantation

Genetic variants in matrix metalloproteinase (MMP) gene may influence the biological function of these enzymes and change their role in carcinogenesis and progression. The effect of MMP2 C-1306T and MMP9 C-1562T polymorphisms on genetic susceptibility has been investigated in various kinds of cancer. However, the relationship between these polymorphisms and risk of recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT) has not been reported. The present study was designed to investigate the association of these two loci with the risk of HCC recurrence in 93 HCC patients treated with LT. Genotyping was performed using direct DNA sequencing. For MMP2 C-1306T variant, patients with CT heterozygous conferred a 58% reduction in recurrence risk (risk ratio: 0.419; 95% confidence interval: 0.177-0.994). The mean recurrence-free survival for CT genotype was significantly longer than that for homozygous CC patients (30.4 vs 19.3 months, p = 0.019). However, no association was found between MMP9 C-1562T polymorphisms and recurrence of HCC (p = 0.259). These findings suggest that MMP2 promoter polymorphisms may provide some predictive value for HCC recurrence after LT.

MMP‐2, ‐3 and ‐9 levels and activity are not related to Aβ load in the frontal cortex in Alzheimer's disease

Matrix metalloproteinases (MMPs) -2, -3 and -9 are up-regulated in several cell types on exposure to amyloid beta peptide (Abeta) and have Abeta-degrading activity in vitro. The aims of this study were to determine (i) the distribution of MMP-2, -3 and -9 in the cerebral cortex in Alzheimer's disease (AD) and control brains; (ii) whether the levels and activity of these proteases are increased in AD; and (iii) whether their activity is related to Abeta load. In addition, we examined whether promoter polymorphisms in the MMP-3 and -9 genes are associated with AD in the study cohort. Paraffin sections of frontal lobe from AD and control cases were immunostained for MMP-2, -3 and -9 and tissue homogenates used for MMP activity assays. DNA from these cases was genotyped for the MMP-3 5A/6A (-1171) and MMP-9 C-1562T promoter polymorphisms. Immunohistochemistry revealed MMP-3 in plaques and both MMP-3 and -9 around scattered neurones. The levels and activity of all three MMPs were similar in AD and control brains and bore no relationship to Abeta load. Analysis of MMP-3 -1171 5A/6A allele frequencies showed that the 6A allele (with reduced promoter activity) was associated with AD; the MMP-9 C-1562T polymorphism was not. The levels and activities of MMP-2, -3 and -9 are not increased in the frontal cortex in AD and are not related to Abeta load. Our findings suggest that altered expression of these proteases does not make a significant contribution to the accumulation of Abeta in AD.

Polymorphism of Matrix Metalloproteinase-3 Promoter Gene as a Risk Factor for Coronary Artery Lesions in Kawasaki Disease

Kawasaki disease (KD) is a major cause of acquired coronary artery diseases in childhood. The serum levels of matrix metalloproteinase (MMP)-3 and MMP-9 in KD have been reported to be significantly higher than other diseases. Several studies have demonstrated that MMP-3 5A/6A polymorphism and MMP-9 C-1562T polymorphism modify each transcriptional activity in allele specific manner. We hypothesized that these polymorphisms may play a role as a risk factor for development of coronary artery lesions (CAL) in KD. Eighty-three patients, diagnosed with KD in Cheju National University Hospital from January 2000 to February 2004, were divided into two groups according to the presence of CAL. Genotyping of MMP-3 and MMP-9 gene polymorphisms were determined by restriction fragment length polymorphism. With regard to MMP-3 gene polymorphism, the KD with CAL group had a higher frequency of 6A/6A genotype than control group (p=0.0127) and the KD without CAL group (p=0.0036). However, no significant differences in the allele and genotype distributions of the MMP-9 polymorphism were observed. These findings suggest that MMP-3 6A/6A genotype may be an independent risk factor for CAL formation in KD.