MMP1 Rs1799750 Research Articles

Germline Variants in Angiogenesis-Related Genes Contribute to Clinical Outcome in Head and Neck Squamous Cell Carcinoma.

Simple SummaryA high risk of relapse and treatment resistance are among the major challenges in locally advanced head and neck squamous cell carcinoma (HNSCC). Data show that common germline alterations in genes regulating angiogenesis may modulate treatment sensitivity, cancer progression, and prognosis, but relatively little is known about their role in HNSCC. Thus, our goal was to examine the effect of variation in these genes on survival outcomes in HNSCC patients receiving radiotherapy and cisplatin-based chemoradiotherapy. We identified genetic variants significantly affecting therapy results, constituting independent prognostic factors in these patients. Our results suggest that some polymorphisms in angiogenesis genes may be determinants of treatment efficacy and tumor aggressiveness in HNSCC, which may be of importance in standard therapy. These findings emphasize the potential value of the host genetic profile related to angiogenesis in assessing the risk of treatment failure.Fibroblast growth factor (FGF)/FGF receptor (FGFR), and platelet-derived growth factor (PDGF)/PDGF receptor (PDGFR) systems, as well as some matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs), are involved in various steps of angiogenesis. Data indicate that common germline variations in angiogenesis-regulating genes may modulate therapy results and cancer progression. However, whether these variants affect clinical outcome in head and neck squamous cell carcinoma (HNSCC) is unclear. Hence, we assessed the relationship between FGF/FGFR, PDGF/PDGFR, MMP, and TIMP genetic variants and treatment outcomes in HNSCC patients receiving radiotherapy (RT) alone or combined with cisplatin-based chemotherapy. In multivariate analysis, FGF2 rs1048201 CC homozygotes showed a higher risk of death (p = 0.039), while PDGFRA rs2228230 T was strongly associated with an increased risk of locoregional relapse (HR 2.49, p = 0.001) in the combination treatment subgroup. In the RT alone subset, MMP2 rs243865 TT carriers had a higher risk of locoregional recurrence (HR 2.92, p = 0.019), whereas PDGFRB rs246395 CC homozygotes were at increased risk of metastasis (HR 3.06, p = 0.041). The MMP2 rs7201 C and TIMP2 rs7501477 T were associated with a risk of locoregional failure in the entire cohort (p = 0.032 and 0.045, respectively). Furthermore, rs1048201, rs2228230, rs246395, rs243865, rs7201, and rs7201/rs7501477 were independent indicators of an unfavorable outcome. This study demonstrates that the FGF2, PDGFRA, PDGFRB, MMP2, and TIMP2 variants may contribute to treatment failure and poor prognosis in HNSCC.

Association between matrix metalloproteinases-2 and -9 gene polymorphism with basement membrane disruption in oral lichen planus: A case-control pilot study

ObjectivesThis study investigated genetic polymorphism of matrix metalloproteinases (MMP) −2 and −9 in oral lichen planus (OLP) and their association with the basement membrane status. Study designThis case-control study involved genotyping of peripheral blood sample of 32 OLP patients and 106 ethnically matched controls. Single nucleotide polymorphisms (SNP) that were assessed in the groups were- MMP9 rs3918242, MMP9 rs17576 and MMP2 rs865094. Basement membrane status of the OLP biopsy samples was microscopically assessed and recorded following Periodic acid Schiff staining. ResultsMMP9 rs3918242 showed significant genotypic and allelic associations between OLP subjects and controls. It was also significantly associated with intact basement membranes in OLP cases with increased frequency of ‘TT’ genotype and ‘T’ allele. No association was found with regard to MMP9 rs17576 and MMP2 rs865094. ConclusionBiallelic substitution at the promoter region of MMP9 (rs3918242) gene may be associated with increased risk of development of OLP. It may be involved in compromising the integrity of the basement membrane junction.

Association of Promoter Polymorphism of MMP-1 rs1799750 and MMP-3 rs3025058 with circulating levels of MMP-1 and MMP-3 in patients with Rheumatoid Arthritis

The genetic background of Rheumatoid arthritis (RA) is only partly understood and several genes seem to be involved. Matrix metalloproteinases (MMPs) are involved in joint destruction in rheumatoid arthritis (RA). MMP1 (interstitial collagenase) and MMP3 (stromelysin 1) as most studied enzymes in RA. In the present study, we have investigated the genotypic and haplotypic relationships of the MMP-1 and MMP-3 genes with circulating levels of these MMPs. Functional relevance in single-nucleotide polymorphisms (SNPs)in rs1799750 (1G/2G, MMP-1 promoter) and rs3025058 (5A/6A, MMP-3 promoter) genotyped in 60 RA patients and 60 healthy control is used to determine association of polymorphisms with the severity of the disease. The MMP-3 SNPs were associated with serum MMP-3 level (P <0.05) and were associated with disease activity score (DAS28). We observed that MMP-1 SNPs were lacking in association with disease activity. Our findings conclude that several closely linked polymorphisms in the MMP-1–MMP-3 loci have an important role in determining the circulating levels of these MMPs in RA and that MMP-3 polymorphism is associated with the disease severity.

Estimation of associations between MMP9 gene polymorphisms and breast cancer: Evidence from a meta-analysis.

Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases, which play critical roles in cancer progression and metastasis. In recent years, many researchers have been studying the relationship between MMP9 and breast cancer. However, it still remains indecisive. Therefore, we conducted a meta-analysis to draw more accurate conclusions. A total of 21 relevant documents were retrieved, including 25 case-control studies. We quantitatively analyzed the data obtained. To clarify the relationship between MMP9 polymorphism and breast cancer susceptibility under different conditions, we also made a further subgroup analysis for each locus. In summary, we discovered that MMP9 rs3918242 rendered an increased risk for breast cancer, especially among Iranians and Indians. MMP9 rs3787268 could be a protective factor. MMP9 rs17576 and MMP9 rs2250889 have no association with breast cancer risk.

Genetic Variants of Matrix Metalloproteinase and Sepsis: The Need Speed Study.

Many causal mechanisms in sepsis susceptibility are largely unknown and the functional genetic polymorphisms (GP) of matrix metalloproteinases (MMPs) and their natural tissue inhibitor of MMPs (TIMP1) could play a role in its development. GPs of MMPs and TIMP (namely MMP-1 rs1799750, MMP-3 rs3025058, MMP-8 rs11225395, MMP-9 rs2234681, and TIMP-1 rs4898) have been compared in 1058 patients with suspected sepsis to assess the association with susceptibility and etiology of sepsis. Prevalence of MMP8 rs11225395 G/G genotype was higher in sepsis patients than in those with non-infective Systemic Inflammatory Reaction Syndrome (35.6 vs. 26%, hazard ratio, HR 1.56, 95% C.I. 1.04–2.42, p = 0.032). G/G patients developed less hyperthermia (p = 0.041), even after stratification for disease severity (p = 0.003). Patients carrying the 6A allele in MMP3 rs3025058 had a higher probability of microbiologically-proven sepsis (HR 1.4. 95%C.I. 1.01–1.94, p = 0.044), particularly when due to virus (H.R. 2.14, 95% C.I. 1.06–4.31, p = 0.046), while MMP-1 G/G genotype patients carried a higher risk for intracellular bacteria (Chlamydia, Mycoplasma, and Legionella, H.R. 6.46, 95% C.I. 1.58–26.41, p = 0.003). Neither severity of sepsis at presentation, nor 30-day mortality were influenced by the investigated variants or their haplotype. MMP8 rs11225395 G/G carriers have lower temperature at presentation and a more than 50% increased susceptibility to sepsis. Among patients with sepsis, carriers of MMP1 rs1799750 G/G have an increased susceptibility for intracellular pathogen infections, while virus serology is more often positive in those with the MMP3 rs3025058 A/A genotype.

Genetic Polymorphism of Matrix Metalloproteinase-9 and Susceptibility to Myocardial Infarction: A Meta-Analysis

Objective Current findings on the association between MMP-9 rs3918242 and susceptibility to myocardial infarction (MI) are inconsistent, and their definite relationship is discussed in this meta-analysis. Methods Eligible literatures reporting MMP-9 rs3918242 and susceptibility to MI were searched in PubMed, Cochrane Library, CNRI, and VIP using keywords such as “MMP-9”, “matrix metallopeptidase-9” and “myocardial infarction”, “acute myocardial infarction”, “AMI”, and “polymorphism”. Data from eligible literatures were extracted for calculating OR and corresponding 95% CI using RevMan 5.3 and STATA12.0. Results Ten independent literatures reporting MMP-9 rs3918242 and susceptibility to MI were enrolled. Compared with subjects carrying CT&TT genotype of MMP-9 rs3918242, susceptibility to MI was lower in those carrying CC genotype (OR = 1.49, 95%CI = 1.19–1.86, P = 0.0004). Such a significance was observed in the overdominant (OR = 1.27, 95%CI = 1.14–1.41, P < 0.0001) and allele genetic models (OR = 1.43, 95%CI = 1.17–1.74, P = 0.0005) as well. This finding was also valid in the Asian population. Conclusions Mutation on MMP-9 rs3918242 has a potential relevance with susceptibility to MI.

Extracellular matrix remodeling in anthracycline-induced cardiotoxicity: What place on the pedestal?

ObjectiveTo evaluate the role of matrix metalloproteinases (MMP)-2 and 9 and the gene polymorphisms of MMP-2 (rs243865) and MMP-9 (rs3918242) in the course of anthracycline-induced cardiotoxicity (AIC) in women without previous cardiovascular diseases (CVD) during 24-months. MethodsA total of 114 women (47.0 [44.0; 52.0] years old) with AIC of NYHA class I-III who received doxorubicin for breast cancer were enrolled. ResultsAfter 24 months patients had breast cancer remission and were divided into 2 groups: group 1 comprised women with adverse course of AIC (n = 54), group 2 comprised those without it (n = 60). Serum levels of MMP-2 were higher by 8% (p = 0.017) MMP9 by 18.4% (p < 0.001) in group 1 than in group 2. In group 1 the levels of MMP-2 increased (p < 0.001) from 376.8 (329.5; 426.7) to 481.4 (389.8; 518.7) pg/mL, and MMP-9 increased (p < 0.001) from 23.6 (21.4; 24.6) to 26.0 (23.3; 27.0) pg/mL at 24 months. In group 2 the both MMP-2 and MMP-9 level decreased at 24 months. Based on ROC-analysis, the levels of MMP2 ≥ 388.2 pg/mL (AUС = 0.64; р = 0.013) and MMP-9 ≥ 21.25 pg/mL (AUС = 0.9; р < 0.001) were identified as predictors for adverse course of AIHF. The presence of C/C genotype of MMP2 (OR = 4.76; p = 0.029) and C/C genotype of MMP-9 (OR = 15.2; p < 0.0001) were related with adverse course of AIHF and higher levels of MMP-2 and MMP-9. ConclusionGene polymorphisms of MMP-2 (rs243865) and MMP-9 (rs3918242) and serum levels of MMP-2 and MMP-9 levels in women without previous CVD were associated with adverse course of AIC during 24 months.

Association of single nucleotide polymorphisms in the CD209, MMP9, TNFA and IFNG genes with susceptibility to Japanese encephalitis in children from North India

Japanese encephalitis (JE), an acute encephalitis syndrome disease caused by infection with JE virus (JEV), is an important mosquito borne disease in developing countries. The clinical outcomes of JEV infection show inter individual differences. Only in a minor percent of the infected subjects, the disease progresses into acute encephalitis syndrome. Single nucleotide polymorphisms in the host immune response related genes are known to affect susceptibility to JE. In the present study, 238 JE cases and 405 healthy controls (HCs) without any known history of encephalitis were investigated for SNPs in the CD209 MX1, TLR3, MMP9, TNFA and IFNG genes which are important in the immune response against JEV by PCR based methods. The results revealed higher frequencies of heterozygous genotypes of CD209 rs4804803, MMP9 rs17576, TNFA rs1800629 and IFNG rs2430561 in JE cases compared to HCs. These SNPs were associated with JE in an over-dominant genetic model (Odds ratio with 95% CI 1.51 (1.09-2.10) for CD209 rs4804803, 1.52 (1.09-2.11) for MMP9 rs17576, and 1.55 (1.12-2.15) for IFNG rs2430561). The association of G/A genotype of TNFA rs1800629 with JE was confirmed in a larger sample size. The results suggest the association of CD209 rs4804803, MMP9 rs17576, IFNG rs2430561 and TNFA rs1800629 polymorphisms with susceptibility to JE.

Genetic polymorphism of matrix metalloproteinase 9 and susceptibility to chronic obstructive pulmonary disease: A meta-analysis.

BackgroundTo systematically analyze the influence of genetic polymorphisms of matrix metalloproteinase 9 (MMP9) on susceptibility to chronic obstructive pulmonary disease (COPD).MethodsRelevant literatures reporting MMP9 and susceptibility to COPD in PubMed, Web of Science, VIP, Wanfang and CNKI databases were searched using the key words "matrix metalloproteinases 9/MMP9, COPD/chronic obstructive pulmonary disease". Data of eligible literatures were extracted and analyzed for the odds ratio (OR) and corresponding 95% CI.ResultsA total of 16 independent studies reporting MMP9-1562C/T and COPD patients were enrolled and analyzed. None of the genetic models revealed the relationship between MMP9-1562C/T and susceptibility to COPD. Subgroup analyses identified lower risk of COPD in Chinese population carrying the TT genotype for theMMP9 rs3918242 relative to those carrying CT and CC genotypes (P=0.03, OR=0.67, 95% CI=0.46-0.97).ConclusionsChinese population carrying the TT genotype for the MMP-9 rs3918242 present lower susceptibility to COPD relative to those carrying CT and CC genotypes.

Remodeling of abdominal aortic aneurysm sac following endovascular aortic repair: association with clinical, surgical, and genetic factors

After successful endovascular aortic repair (EVAR), abdominal aortic aneurysms (AAA) sac will undergo negative remodeling (i.e., shrinkage) as a measure of successful exclusion. Determinants of shrinkage after EVAR are not fully known.In 84 post-EVAR patients, time course of AAA diameter after repair and occurrence of endoleaks (ELs) have been correlated with clinical history, medications, anthropometric data, vascular anatomy, and matrix metalloprotease (MMP) genetic variants (namely MMP-1 rs1799750, MMP-3 rs35068180, MMP-9 rs2234681, rs917576, rs917577, MMP-12 rs652438, and TIMP1 rs4898).During follow-up, 41 ELs were detected in 37 patients (44%, 10.4 events/100 pt./y), accounting for AAA dilation or reduced shrinkage (P < .001). High-flow ELs (type 1 and/or 3) occurrence was associated with warfarin use, MMP9 rs17577 polymorphism, and unfavorable anatomy, while low-flow type 2 ELs occurred more often in TIMP1 rs4898 non-T carriers. In EL-free patients, AAA diameter decreased for the first three years, (-4, -3 and - 2 mm/year respectively) and remained stable thereafter. Shrinkage between two measurements (n = 120) was associated with smaller AAA diameter at the baseline, peripheral arterial disease (PAD), patients’ older age at intervention, and G-/G- genotype in MMP1 rs1799750 (binary logistic regression, P = .0001).Aneurysmal sac shrinking occurs for few years after EVAR, only in patients without EL, and is related to older age, PAD, smaller aneurysm size and putative lower MMP1 expression while EL occurrence prevents such a remodeling and is mainly related to local-acting factors like unfavorable anatomy, anticoagulation, and MMP9 and TIMP1 genetic polymorphisms.

The genetic association with injury risk in male academy soccer players depends on maturity status.

It is currently unknown if injury risk is associated with genetic variation in academy soccer players (ASP). We investigated whether nine candidate single nucleotide polymorphisms were associated (individually and in combination) with injury in ASP at different stages of maturation. Saliva samples and one season's injury records were collected from 402 Caucasian male ASP from England, Spain, Uruguay, and Brazil, whose maturity status was defined as pre- or post-peak height velocity (PHV). Pre-PHV COL5A1 rs12722 CC homozygotes had relatively higher prevalence of any musculoskeletal soft tissue (22.4% vs. 3.0%, p=0.018) and ligament (18.8% vs. 11.8%, p=0.029) injury than T-allele carriers, while VEGFA rs2010963 CC homozygotes had greater risk of ligament/tendon injury than G-allele carriers. Post-PHV IL6 rs1800795 CC homozygotes had a relatively higher prevalence of any (67.6% vs. 40.6%, p=0.003) and muscle (38.2% vs. 19.2%, p=0.013) injuries than G-allele carriers. Relatively more post-PHV EMILIN1 rs2289360 CC homozygotes suffered any injury than CT and TT genotypes (56.4% vs. 40.3% and 32.8%, p=0.007), while the "protective" EMILIN1TT genotype was more frequent in post- than pre-PHV ASP (22.3 vs. 10.0%, p=0.008). Regardless of maturity status, T-alleles of ACTN3 rs1815739 and EMILIN1 rs2289360 were associated with greater absence following ankle injury, while the MMP3 rs679620T-allele and MYLK rs28497577 GT genotype were associated with greater absence following knee injury. The combination of injury-associated genotypes was greater in injured vs. non-injured ASP. This study is the first to demonstrate that a genetic association exists with injury prevalence in ASP, which differs according to maturity status.

Correlation of TP53 (rs1625895), TP73 (rs3765730), MMP9 (rs17576), and MTHFR (rs868014) polymorphisms with low ovarian reserve

Objective:To investigate the influence of the Single Nucleotide Polymorphisms (SNPs) TP53 rs1625895, TP73 rs3765730, MMP9 rs17576, and MTHFR rs868014 on ovarian reserve (OR) in infertile patients. Study design:A prospective cross-sectional study was carried out in 145 infertile women. The patients were divided into two groups according to ovarian reserve, characterized by association between AMH levels and AFC:-Group I: 86 patients defined as having low OR (LOR) by AMH < 1 ng/mL + AFC ≤ 9.-Group II: 59 patients defined as having normal OR (NOR) by AMH > 2 ng/mL + AFC ≥ 15.After patient distribution, both groups were compared (LOR X NOR) regarding the genotypes of the SNPs TP53 T/C rs1625895, TP73 G/A rs3765730, MMP9 Gln/Arg rs17576, and MTHFR A/G rs868014. Result(s):The frequency of the TP53-T/T genotype was greater in the LOR and the TP53-C/C genotype was more frequent in patients with NOR. This association was confirmed by the frequency of alleles, where the presence of the T allele was significantly higher in patients who exhibited LOR (P = 0.0003). The frequency of the TP73-G/G genotype and of the G allele was higher in the LOR group (P = 0.01). Considering the MMP9 gene, the frequency of the Gln/Gln genotype was higher in the LOR group. However, the Gln/Arg genotype and the Arg allele prevailed in the NOR group (P = 0.006). The frequency of the MTHFR-A/A genotype was higher in the LOR group, whereas that of the MTHFR-GG genotype was higher in the NOR group. The presence of allele A was significantly higher in the LOR group (P = 0.002). The regression analysis shows that patients who present the TP53-T/T, TP73-G/G, MMP9-Gln/Gln, and MTHFR-A/A genotypes are 3.6X, 3.1X, 3.2X, and 3.7X more likely of having LOR, respectively. In addition, the association of the TP53/TT + TP73/GG genotypes increased the chance of women being included in the LOR group in 5.7-fold. Conclusion(s):The genotypes TP53-T/T, TP73-G/G, MMP9-Gln/Gln, and MTHFR-A/A increase the chance of women to exhibit LOR. These polymorphisms could be useful as genetic markers of low ovarian reserve in infertile patients.

Polymorphisms of matrix metalloproteinases affect the susceptibility of esophageal cancer: Evidence from 20412 subjects, systematic review and updated meta-analysis.

The results of how matrix metalloproteinases (MMPs) polymorphisms affect esophageal cancer (EC) risk are not consistent, especially for MMP1,2,7 and 9. A meta-analysis focused on the impact of MMPs to digestive cancers, but not a precise analysis to EC, therefore, we designed the current study to make a clear understanding of the association between MMPs polymorphisms and EC. Up to March 2020, we searched several databases to find case-control cohorts concerned about the risk of MMPs polymorphisms to EC risk. Odds ratios with 95% confidence intervals under five genetic models to generate the risk predicted value. The Q test and I2 statistics are used to estimate heterogeneity. Sensitivity analysis, Egger test, and Begg's funnel plot were employed to assess the results. In-silico analysis was performed to study the association between the polymorphism and mRNA expression. 19 case-control studies were enrolled, including 8371 EC patients and 12041 health controls. We observed the increased risk in BA vs. AA and BB + BA vs. AA models of MMP1-rs1799750 polymorphism. The protective effectiveness of EC was found in the MMP2 rs243865 polymorphism in B vs. A, BA vs. AA, and BB + BA vs. AA models. Meanwhile, the risk effect was also observed in the MMP7 rs11568818 polymorphism in most genetic models. In the furthermore bioinformatics analysis, we found that MMP1, MMP3, MMP7, MMP9, MMP12, MMP13 all increased in the tumor tissues, and the genetic alteration in the polymorphisms could impact the mRNA expression of the above MMPs. MMP1 rs1799705 and MMP7 rs1156818 polymorphisms will take part in the tumorigenesis of EC, while MMP2 rs243865 acts as a protective role to decrease the risk of EC.

Association of the functionally significant polymorphisms of the MMP9 gene with H. pylori-positive gastric ulcer in the Caucasian population of Central Russia.

Background and purposeThe study analyzed the association of functionally significant polymorphisms of matrix metalloproteinases (MMPs) genes with the development of gastric ulcer (GU) in Caucasians from Central Russia.MethodsThe 781 participants, including 434 patients with GU (196 Helicobacter pylori (H. pylori)-positive and 238 H. pylori-negative) and 347 controls (all H. pylori-negative) were recruited for the study. Ten SNPs of the MMP1 (rs1799750), MMP2 (rs243865), MMP3 (rs679620), MMP8 (rs1940475), and MMP9 (rs3918242, rs3918249, rs3787268, rs17576, rs17577, and rs2250889) genes were considered for association with GU using multiple logistic regression. The SNPs associated with GU and loci linked (r2≥0.8) to them were analyzed in silico for their functional assignments.ResultsThe SNPs of the MMP9 gene were associated with H. pylori-positive GU: alleles C of rs3918249 (OR = 2.02, pperm = 0.008) and A of rs3787268 (OR = 1.60–1.82, pperm ≤ 0.016), and eight haplotypes of all studied MMP9 gene SNPs (OR = 1.85–2.04, pperm ≤ 0.016) increased risk for H. pylori-positive GU. None of the analyzed SNPs was independently associated with GU and H. pylori-negative GU. Two haplotypes of the MMP9 gene (contributed by rs3918242, rs3918249, rs17576, and rs3787268) increased risk for GU (OR = 1.62–1.65, pperm ≤ 0.006). Six loci of the MMP9 gene, which are associated with H. pylori-positive GU, and 65 SNPs linked to them manifest significant epigenetic effects, have pronounced eQTL (17 genes) and sQTL (6 genes) values.ConclusionSNPs of the MMP9 were associated with H. pylori-positive GU but not with H. pylori-negative GU in Caucasians of Central Russia.

Matrix metalloproteinase-2 and angiotensin-1 gene polymorphisms in patient who have coronary artery disease

Introduction: The rupture of atherosclerotic plaques is caused by the impact of matrix metalloproteinases (MMPs) upon the local fibrous valve and so might convert a chronic disease to a myocardial infarction, ultimately leading to instant death. Angiotensin converting enzyme (ACE) is actively engaged in the pathogenesis of ischemic heart disease. This study tries to unravel whether/how ACE and MMP-2 gene polymorphism contributes to the occurrence of Coronary Artery Disease (CAD). Materials and methods: A total of 300 individuals (100 healthy/200 patients) were included in the study. A PCR-RFLP method was utilized for ACE gene I/D and DNA sequencing MMP-2 (-1306 C/T) polymorphisms. Results: The ACE-1 gene D/D, I/D and I/I genotype frequency of the CAD cohort was 50%, 29%, and 21%, respectively whereas that of the healthy control cohort was 37%, 45% and 18%, respectively. Our findings indicate that the groups differed significantly in relation to the ACE-1 genotypes (p=0.021). The frequencies of ACE-1 gene allele I and D in both cohorts did not reveal a significant difference (p=0.314). In addition, the two groups did not manifest MMP-2 (rs243865) gene polymorphism. Conclusion: The association between MMP-2 gene polymorphism and CAD is too weak to suggest a conclusive evidence. The I/D genotype frequency remained higher in the healthy individuals than in the CAD cohort, while in the CAD group D/D genotype was more frequently than control group. Finally, the patients with D/D genotype tend to bear greater risk for cardiovascular diseases.

The Role of MMP-9 rs 3918242 genetic variant in association between MMP-9 serum level with risk factors of acute ischemic stroke

Background: Increased serum MMP-9 level is known to be biomarker of atherosclerotic events and risk of cerebrovascular disease. Risk factors for acute ischemic stroke are known to be related to serum MMP-9 level. The genetic variant of MMP-9 rs3918242 is known to have a role in serum MMP-9 level. The aim of the study is to determine the role of MMP-9 rs 3918242 genetic variant in association between MMP-9 serum level with risk factors of acute ischemic stroke.Methods: This was a cross-sectional study with an observational analytic design. 62 subjects of acute ischemic stroke treated at Dr. Kariadi Hospital Semarang from October 2018 to February 2019 were involved in this study. Statistical analysis was assessed by the bivariate test and followed by a logistic regression test.Results: From 62 subjects in this study, 45 (72.6%) had high serum MMP-9 level. The association between serum MMP-9 level with risk factors of acute ischemic stroke was statistically significant in hypertension, diabetes mellitus, dyslipidemia, obesity, and hyperuricemia. There is a positive correlation of serum MMP-9 level with a number of acute ischemic stroke factors. In multivariate analysis, the most influential variables were obesity and hyperuricemia. CC Genetic Variant has a role in the association between serum MMP-9 level with risk factors of acute ischemic stroke, which are hypertension, diabetes mellitus, dyslipidemia, obesity, and hyperuricemia. Meanwhile, CT genetic variants only play a role in the association of serum MMP-9 levels with obesity and hyperuricemia as the risk factors for acute ischemic stroke,Conclusion: CC genetic variants with high serum MMP-9 levels are associated with more acute ischemic stroke risk factors than CT genetic variants with high MMP-9 serum levels. Therefore, CC genetic variants have the potential to pose more risk of acute ischemic stroke.

Association between idiopathic recurrent pregnancy loss and genetic polymorphisms in cytokine and matrix metalloproteinase genes.

Recurrent reproductive loss (RPL) is a global health issue affecting a significant number of women. Approximately half of miscarriages have an unexplained etiology. Familial aggregation and twins studies prove that some cases of the RPL could have a genetic background. Recent evidences suggest that cytokines (e.g. IL-6, TNF alpha or TGF beta) and matrix metalloproteinases (MMP) are important for maintenance of pregnancy. Single gene polymorphisms (SNP), affecting these proteins production or their function may predispose to the loss of the pregnancy. The aim of this study was to evaluate the association between the following polymorphisms of IL6 (rs1800795), TNF (rs1800629), TGFB1 (rs1800471), MMP1 (rs1799750), MMP2 (rs2285053 and rs243865), MMP3 (rs35068180), MMP9 (rs3918242) and the recurrent pregnancy loss in polish population. Study subjects comprised of 67 patients with a history of recurrent pregnancy loss (≥ 2 miscarriages in history) and 75 controls. The distribution of genotypes for selected polymorphisms were determined by RFLP-PCR. Maternal genotypes GG TNF, or 5A/5A MMP3 may be associated with the recurrent pregnancy loss. No association between the IL6, TGFB1, MMP1, MMP2, or MMP9 studied polymorphisms and the predisposition to miscarriage was found. This study demonstrated a possible association between rs1800629 TNF, rs35068180 MMP3 polymorphisms and recurrent pregnancy loss.

Impact of MMP2 rs243865 and MMP3 rs3025058 Polymorphisms on Clinical Findings in Alzheimer's Disease Patients.

Alzheimer's disease (AD) is a chronic neurodegenerative disease of the central nervous system with higher prevalence in elderly people. Despite numerous research studies, the etiopathogenesis of AD remains unclear. Matrix metalloproteinases (MMPs) are endopeptidases involved in the cleavage of extracellular matrix proteins and basement membrane compounds. In the brain, the pathological role of MMPs includes the disruption of the blood-brain barrier leading to the induction of neuroinflammation. Among various MMPs, MMP-2 and MMP-3 belong to candidate molecules related to AD pathology. In our study, we aimed to evaluate the association of MMP2 rs243865 and MMP3 rs3025058 polymorphisms with AD susceptibility and their influence on age at onset and MoCA score in patients from Slovakia. Both MMP gene promoter polymorphisms were genotyped in 171 AD patients and 308 controls by the PCR-RFLP method. No statistically significant differences in the distribution of MMP2 rs243865 (-1306 C>T) and MMP3 rs3025058 (-1171 5A>6A) alleles/genotypes were found between AD patients and the control group. However, correlation with clinical findings revealed later age at disease onset in MMP2 rs243865 CC carriers in the dominant model as compared to T allele carriers (CC vs. CT+TT: 78.44 ± 6.28 vs. 76.36 ± 6.39, p = 0.036). The results of MMP3 rs3025058 analysis revealed that 5A/6A carriers in the overdominant model tended to have earlier age at disease onset as compared to other MMP3 genotype carriers (5A/6A vs. 5A/5A+6A/6A: 76.61 ± 5.88 vs. 78.57 ± 6.79, p = 0.045). In conclusion, our results suggest that MMP2 rs243865 and MMP3 rs3025058 promoter polymorphisms may have influence on age at onset in AD patients.

Association of the MMP-3, MMP-9 and MMP-12 gene polymorphisms with COPD risk: a meta-analysis.

Given the evidence that the matrix metalloproteinases (MMPs) play an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD), a number of case-control studies have attempted to assess the relationship between genetic polymorphisms in MMP genes and COPD risk. However, reliable measures of these results are lacking. We assessed the published evidence for association of the MMP-3, MMP-9 and MMP-12 polymorphisms with COPD risk using meta-analytic techniques. The odds ratio (OR) and 95% confidence interval (CI) were calculated for each study using fixed or random effect models. A total of 23 case-control studies were included in the meta-analysis. No significant association was observed between the MMP-9 rs3918242 polymorphism and COPD risk in the overall populations under the dominant (T/T + C/T vs. C/C: OR = 1.30, 95% CI: 1.00-1.69, p = 0.054) and allele contrast (T allele vs. C allele: OR = 1.22, 95% CI: 0.97-1.53, p = 0.088) models. However, in sub-group analysis the polymorphism rs3918242 was significant in Asians under the dominant model (T/T + C/T vs. C/C: OR = 1.66, 95% CI: 1.02-2.72, p = 0.043). The results for MMP-12 rs2276109 showed an association with COPD only in mixed populations (G/G + A/G vs. A/A: OR = 1.57, 95% CI: 1.10-2.24, p = 0.013; G allele vs. A allele: OR = 1.52, 95% CI: 1.09-2.14, p = 0.015). We did not find any significant association of the MMP-12 rs652438 and MMP-3 rs35068180 polymorphisms with COPD. The findings of this meta-analysis suggest that there is a risk of COPD associated with the MMP-9 rs3918242 and MMP-12 rs2276109 polymorphisms in certain ethnic groups.

The 1G/1G+1G/2G Genotypes of MMP1 rs1799750 Are Associated with Higher Levels of MMP-1 and Are Both Associated with Lipodystrophy in People Living with HIV on Antiretroviral Therapy.

In HIV-infected patients, antiretroviral therapy (ART) is associated to adipose tissue redistribution known as lipodystrophy (LD). This study aimed at verifying the association between the polymorphism of the MMP1 gene (rs1799750) (1G/2G) and the serum levels of matrix metalloproteinase 1 (MMP-1) with LD and its subtypes in people living with HIV on ART. This is a cross-secional study. LD was self-reported. The determination of the MMP1 rs1799750 gene polymorphism was performed by real-time PCR, and the serum concentrations of MMP-1 were quantified by the enzyme-linked immunosorbent assay (ELISA) method. Of 404 participants, 204 (51%) were diagnosed with LD, of whom 89 (43%) had mixed lipodystrophy (ML), 72 (35%) had lipohypertrophy (LH), and 43 (22%) had lipoatrophy (LA). There was an association between the genotypes 1G/1G+1G/2G and higher serum levels of MMP-1 (p = .025). There was no association of MMP1 (1G/2G) with LD. Other factors associated with LD were current CD4 ≤ 350 [odds ratio (OR) = 4.85, confidence interval (CI) = 1.78-47.99, p = .0033] and serum MMP-1 levels >6.81 (OR = 2.67, CI = 1.21-6.08, p = .0165). Factors associated with ML: current CD4 ≤ 350 (OR = 5.59, CI = 1.69-20.39, p = .006); with LH: number of antiretroviral regimens used: 2 (OR = 2.06, CI = 1.01-4.20, p = .0460) and 3+ (OR = 2.09, CI = 1.00-4.35, p = .0477), and current CD4 ≤ 350 (OR = 2.08, CI = 1.00-4.24, p = .0461); and with LA: current viral load >40 (OR = 2.52, CI = 1.03-5.91, p = .0372) and current use of zidovudine (OR = 2.97, CI = 1.32-6.54, p = .0074). Higher levels of MMP-1 were associated with genotypes 1G/2G+1G/1G and with LD. Other individual risk factors were independently associated with LD, and its subtypes, suggesting that the pathogenesis itself is differently manifested for each type of LD.