MMP-9 Polymorphisms Research Articles

Association of MMP-1 (rs1799750)-1607 2G/2G and MMP-3 (rs3025058)-1612 6A/6A Genotypes With Coronary Artery Disease Risk Among Iranian Turks.

The study was conducted to evaluate the association between MMP-1 (rs1799750)-1607 1G/2G and MMP-3 (rs3025058)-1612 5A/6A polymorphisms/haplotypes and coronary artery disease (CAD) risk among Iranian Turks. Totally, 102 patients with CAD and 102 healthy subjects joined the study. Genomic DNA isolation was carried out using "salting out" method from 3 to 4 mL of whole blood samples. The MMP-1 (-1607 2G/1G) and MMP-3 (-1612 5A/6A) promoter gene polymorphisms were detected via polymerase chain reaction restriction fragment length polymorphism. Our results indicated that the frequencies of the MMP-1 (-1607) 2G alleles and 2G/2G genotypes and the MMP-3 (-1612) 6A alleles and 6A/6A genotypes were higher in CAD patients older than 50 years than in healthy controls (P < 0.05). We failed to show statistically significant differences between the CAD patients younger than 50 years and controls concerning MMP-1 -1607 ins/delG (1G > 2 G, rs1799750) and MMP-3 -1612 ins/delA (5A/6A, rs3025058) polymorphisms (P > 0.05). The frequencies of MMP-3/MMP-1 haplotypes were not statistically different among tested groups (P > 0.05). This examination, as the first study of its own kind in Iranian Turks, reported association between MMP-1 (rs1799750) -1607 2G/2G and MMP-3 (rs3025058) -1612 6A/6A genotypes and CAD risk in patients older than 50 years.

MMP2 Polymorphism Affects Plasma Matrix Metalloproteinase (MMP)-2 Levels, and Correlates with the Decline in Lung Function in Hypersensitivity Pneumonitis Positive to Autoantibodies Patients.

Among hypersensitivity pneumonitis (HP) patients have been identified who develop autoantibodies with and without clinical manifestations of autoimmune disease. Genetic factors involved in this process and the effect of these autoantibodies on the clinical phenotype are unknown. Matrix metalloproteinases (MMPs) have an important role in architecture and pulmonary remodeling. The aim of our study was to identify polymorphisms in the MMP1, MMP2, MMP9 and MMP12 genes associated with susceptibility to HP with the presence of autoantibodies (HPAbs+). Using the dominant model of genetic association, comparisons were made between three groups. For rs7125062 in MMP1 (CC vs. CT+TT), we found an association when comparing groups of patients with healthy controls: HPAbs+ vs. HC (p < 0.001, OR = 10.62, CI 95% = 4.34–25.96); HP vs. HC (p < 0.001, OR = 7.85, 95% CI 95% = 4.54–13.57). This rs11646643 in MMP2 shows a difference in the HPAbs+ group by the dominant genetic model GG vs. GA+AA, (p = 0.001, OR = 8.11, CI 95% = 1.83–35.84). In the linear regression analysis, rs11646643 was associated with a difference in basal forced vital capacity (FVC)/12 months (p = 0.013, β = 0.228, 95% CI95% = 1.97–16.72). We identified single-nucleotide polymorphisms (SNPs) associated with the risk of developing HP, and with the evolution towards the phenotype with the presence of autoantibodies. Also, to the decrease in plasma MMP-2 levels.

Association of polymorphisms in IL-8, MMP-1 and MMP-13 with the risk and prognosis of oral and oropharyngeal squamous cell carcinoma

ObjectiveThis study investigated the risk and prognostic value of single nucleotide polymorphisms (SNP) inIL-8, MMP-1 and MMP-13 in oral and oropharyngeal squamous cell carcinomas (SCCs). DesignSNPs rs2227532 and rs4073 inIL-8, rs2071230 and rs470558 in MMP-1, and rs2252070 in MMP-13 were genotyped in 125 oral and oropharyngeal SCC patients and 130 healthy controls, using TaqMan allelic discrimination assays. Multiple logistic regression models were used to explore the association between SNPs and cancer development, as well as SNP-SNP interaction and gene-environmental factor (GxE) interaction. Univariate and multivariate methods were applied for survival analyses. ResultsWith exception of rs2227532, all the SNPs were in Hardy-Weinberg equilibrium in the control. No associations between rs4073 in IL-8 and rs2071230 and rs470558 in MMP-1 were observed, but rs2252070 in MMP-13, in the dominant model, was associated in a protective manner to oral and oropharyngeal SCC (OR: 0.20, 95% CI: 0.06-0.71, p = 0.007). All SNPs interact significantly with cigarette smoking and alcohol consumption on susceptibility to oral and oropharyngeal SCC, but they showed no influence on survival of the patients. ConclusionsOur results show that rs2252070 inMMP-13 may confer protection effect against oral and oropharyngeal SCC. In addition, the combined effects of IL-8 (rs4073), MMP-1 (rs2071230 and rs470558) and MMP-13 (rs2252070) with environmental carcinogens, such as tobacco and alcohol, are related to increased risk for oral and oropharyngeal SCC development.

Correlations of MMP-3 and MMP-9 gene polymorphisms with diabetic retinopathy.

Correlations of MMP-3 and MMP-9 gene polymorphisms with diabetic retinopathy.

Polymorphisms in MMP-14 and MMP-2 genes and ovarian cancer survival.

Functional polymorphisms in matrix metalloproteinases can increase or decrease the risk of cancer. This study focused on ovarian cancer and investigated how polymorphisms in the coding region of MMP-14 and the promoter region of MMP-2 are related to clinical characteristics including survival. In 144 patients with ovarian tumours from a Caucasian population, polymorphisms of MMP-14 (+7096 and +6767) and MMP-2 (-735 and -1306) were analysed. These results were then correlated to the immunohistochemical expression of MMP-14 and MMP-2 and clinical characteristics. In these patients, the MMP-14 +7096 polymorphism showed only TT genotype, in sharp contrast to the described MAF (minimal allele frequency) C of 27%. The MMP-14 +6767 G>A polymorphism was found to have a hazard ratio of 2.09 (CI 1.00-4.35, p 0.046) for recurrence-free survival in advanced-stage patients. However, this significance disappeared after Bonferroni correction for multiple testing. No other correlations between MMP-14 and MMP-2 polymorphisms, immunohistochemistry and clinical characteristics were found, except between the MMP-2 -1306 polymorphism and differentiation grade, with a Spearman correlation coefficient of -0.19, p 0.064. In ovarian cancer, the MMP-14 +6767 G>A polymorphism in the coding region seems to improve recurrence-free survival with a hazard ratio of 2.09 (CI 1.00-4.35, p 0.046). However, as this significance disappeared after correction for multiple testing, there is a need for further research on the functional effect of this change in the MMP-14 gene with larger patient sample sizes.

The relationship between single nucleotide polymorphisms and dental implant loss: a scoping review.

ObjectivesThe purpose of this review was to evaluate the relationship between genetic polymorphisms and dental implant loss.Materials and methodsAll case-control studies examining single nucleotide polymorphisms (SNPs) and dental implant failure were considered. A Boolean search was conducted on PubMed and Scopus to find eligible studies.ResultsThe initial search produced 78 results. Twenty-one studies were considered for inclusion after review and 16 were included in the final review. Twenty-two different polymorphisms were analyzed and statistically significant correlation was found for IL-4, IL-1A, IL-1B, MMP-8, and MMP-1 polymorphisms for dental implant failure.DiscussionA limited number of comprehensive studies have been done in this field. Additional studies with larger sample sizes and different ethnic backgrounds need to be done to see if the results can be reproduced. Of the polymorphisms studied, the IL-4 (+33), MMP-8 (−799), MMP-1 (−519), and MMP-1 (−1607) polymorphisms show the greatest association with dental implant loss.

IL18 Polymorphism and Periodontitis Susceptibility, Regardless of IL12B, MMP9, and Smoking Habits.

Genetic variations contribute to the susceptibility in the development of periodontitis. The aim of this study was to investigate the influence of IL18, IL12, and MMP9 polymorphisms in the chronic periodontitis. This case-control study involved 381 individuals matched by gender and age. Genotyping of IL18 (rs187238 and rs1946518) and IL12B (rs3212227) was performed by PCR-SSP and PCR-RFLP was used for MMP9 (rs3918242). IL-18 and MMP-9 were quantified in the serum by ELISA. SNPStats and OpenEpi software were used for statistical analysis and, in order to eliminate smoking as a confounding factor, the analyses were also performed in nonsmoking subjects. The IL18-137G/C genotype was associated with the risk of chronic periodontitis in nonsmokers (Pc = 0.03; OR = 1.99; overdominant inherence model). In the multivariate analyses, homozygous IL18-137G/G and IL18-607C/C were more frequent in males compared to women with these same genotypes (OR = 2.51 and OR = 3.30, respectively). The serum levels of the IL-18 in patients were higher than those in healthy controls (P = 0.005). IL12B and MMP9 polymorphisms and MMP-9 serum concentration were similar in patients and controls. In this study, IL18 was associated with chronic periodontitis susceptibility. Men had greater risk than women for developing the disease when IL18 polymorphism was considered and the susceptibility was independent of the smoking status.

Role of MMP-2(-1306 C/T) and TIMP-2(-418G/C) Polymorphism in Chinese Han Patients with Acne Vulgaris.

Acne is the most common chronic inflammatory skin diseases. Multiple factors, such as hormonal, environmental, immunological, and genetic factors, are thought to be involved in acne. However, genetic studies have yet to elucidate the full mechanism of acne. The aim of this study was to investigate the association of MMP-2 (-1306C/T) and TIMP-2 (-418G/C) polymorphisms with the risk of acne vulgaris in a Chinese Han population. We also analyzed the correlation of clinical parameters and family history in patients with acne vulgaris. This study included 251 acne patients and 121 age- and sex-matched healthy controls. Genomic DNA was extracted from peripheral blood, and genotyping was performed by PCR and DNA sequencing techniques. There is a significant correlation between the MMP-2 (-1306C/T) polymorphism and the acne vulgaris (P<0.001). Although no association was found between the TIMP-2 (-418G/C) polymorphism and the acne vulgaris, patients with the MMP-2 CT/TIMP-2 GG or GC allele are at higher risk of acne vulgaris. There is also a significant difference in the severity of the disease between acne vulgaris patients with and without family history (P<0.001). This study indicated that the MMP-2 (-1306C/T) polymorphism, in combination with the TIMP-2 (-418G/C) polymorphism, contributes to acne vulgaris susceptibility in the Chinese Han population.

Association of MMP9-1562C/T and MMP13-77A/G Polymorphisms with Non-Small Cell Lung Cancer in Southern Chinese Population.

Background: Matrix metalloproteinases (MMPs) are capable of degrading and modifying most components of the extracellular matrix (ECM) and the basal membrane (BM), and play crucial roles in cancer invasion and metastasis. MMP gene expressions were regulated primarily at the transcriptional level, which was associated with tumor spread and patient prognosis. Polymorphisms in MMPs have been reported to be associated with non-small cell lung cancer (NSCLC). The objective of this study aim to evaluate the serum levels and polymorphisms of MMP-9 and MMP-13 in non-small cell lung cancer patients compared to normal subjects and their correlation to non-small cell lung cancer histopathology findings in Southern Chinese people. Methods: This case–control study included 245 patients with NSCLC and 258 healthy controls. Genomic DNA was extracted by using DNA extraction kit, genotyping was confirmed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and direct DNA sequencing, and serum levels of MMP-9 and MMP-13 were measured by using a specific ELISA, Human Matrix Metalloproteinase Enzyme Immunoassay Kits. Statistical analysis was carried out using the SPSS 23.0 software package. Results: The subjects carrying the TT genotype had a decreased risk of lung cancer in MMP9-1562C/T comparing with the CC genotype (p = 0.00, OR = 0.45, 95% CI = 0.29–0.68), and the MMP13-77 AA genotype was associated with a decreased risk of NSCLC by comparing with the GG genotype (p = 0.03, OR = 0.56, 95% CI = 0.33–0.94). Moreover, the C allele of MMP9-1562C/T could increase serum level of NSCLC in compared with the A allele (OR = 1.19, 95% CI = 0.75–1.89). Similarly, the AA genotype of MMP13 might be a marker of decreased serum level of lung cancer (OR = 0.76, 95% CI = 0.51–1.14). Conclusions: The results of these analyses underline the support of the notion that the CC genotype of MMP9-1562C/T and GG genotypes of MMP13-77G/A were associated with the increased risk NSCLC, and the serum levels of MMP9 and MMP13 were consistent with the results of the SNP analysis. MMP13 and MMP9 might be function as a key oncogene in NSCLC with a Southern Chinese population. Combined detection of SNP and enzyme activity between MMP9 and MMP13 are expected to be a potential diagnostic method of non-small cell lung cancer.

Meta-analysis of the rs243865 MMP-2 polymorphism and age-related macular degeneration risk.

PurposeSeveral researchers have suggested that the rs243865 (16q13-q21) polymorphism in the promoter region of the metalloproteinase-2 (MMP-2) gene could be associated with an increased risk of developing age-related macular degeneration (AMD). However, previous results remain inconclusive. To clarify this controversy, we conducted a meta-analysis of the relationship between rs243865 of MMP-2 and AMD.MethodsWe included 6 independent case-control studies involving 1,682 AMD patients and 2,295 healthy subjects. The association between the rs243865 polymorphism and AMD was examined by the overall odds ratio (OR) with a 95% confidence interval (CI). We used a recessive genetic model analysis, sensitivity analysis, and assessment of bias in our meta-analysis.ResultsOur results showed that there was no significant association between the variant T allele (p-value = 0.10, OR [95%CI] = 0.95 [0.82–1.10]) or the CT+TT genotype (p-value = 0.16, OR [95%CI] = 0.92 [0.76–1.12]) of rs243865 MMP-2 polymorphism and the presence of AMD.ConclusionsThe rs243865 MMP-2 polymorphism was not associated with an increased risk of developing AMD. The MMP-2 (-1306 C>T) promoter variant is unlikely to have a major role in AMD risk susceptibility.

Association of Matrix Metalloproteinase 9 (MMP-9) Polymorphisms with Asthma Risk: A Meta-Analysis.

Published data on the association between MMP-9 polymorphisms (−1562 C > T, rs3918242; Gln279Arg, rs17576 Arg668Gln, rs17577) and asthma susceptibility are inconclusive. To derive a more precise estimation of this association, a meta-analysis was performed. A literature search was conducted in PubMed, Web of Science, EMBASE, Wanfang, and China National Knowledge Infrastructure (CNKI) databases to identify eligible studies. The pooled odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were used to calculate the strength of association. Sensitivity analysis was performed to evaluate the influence of individual studies on the overall effect estimates, and funnel plots and Egger's test were inspected for indication of publication bias. Seven studies with 1592 asthma patients and 1987 controls were finally identified. Overall, we found no significant association between −1562 C > T, rs3918242 polymorphism, and asthma susceptibility in any of the genetic model comparisons. After categorizing studies into different subgroups on the basis of ethnicity and age, there is still no significant association. For the Gln279Arg, rs17576 polymorphism, there seems to be a significant association in the allelic genetic model in regard to the P value (OR = 1.11, 95% CI = 1.00–1.22, I 2 = 0%, P (Z)=0.044); however, the value of lower 95% CI is 1.0. For the Arg668Gln, rs17577 polymorphism, a high significant association was observed in the dominant model comparison (OR = 1.65, 95% CI = 1.28–2.11, I 2 = 22.50%, P (Z)=0), recessive model comparison (OR = 2.40, 95% CI = 1.23–4.72, I 2 = 0%, P (Z)=0.011), homozygote genotype comparison (OR = 2.69, 95% CI = 1.36–5.33, I 2 = 0%, P (Z)=0.004), and allelic genetic model (OR = 1.59, 95% CI = 1.29–1.97, I 2 = 36.9%, P (Z)=0). Sensitivity analysis demonstrated the stability of our results, and publication bias was not evident. The present meta-analysis suggests that MMP-9 Arg668Gln, rs17577 polymorphism may be the risk factor for asthma susceptibility.

The relationship between MMP9 and ADRA2A gene polymorphisms and mothers\u2013newborns\u2019 nutritional status: an exploratory path model (STROBE compliant article)

BackgroundThe aim of this study was to evaluate the direct effects of matrix metalloproteinase (MMP9 rs17577, MMP9 rs17576) and alfa 2 adrenergic receptor (ADRA2A rs553668) gene polymorphisms investigated in mothers and their newborns on maternal weight gain (MWG) during pregnancy and the newborn’s birth weight (BW), taking into account the presence of other related factors.MethodsWe performed a cross-sectional study in 197 mother–newborn pairs in an Obstetrics Gynecology Clinic, in order to evaluate the demographic and anthropometric parameters, and gene polymorphism.ResultsBW was positively correlated with maternal age (p = 0.021) and the educational level (p = 0.002), and negatively correlated with smoking status in pregnant women (p < 0.001). The MMP9 rs17577 variant genotypes in mothers led to a lower BW (p = 0.049). The mothers with a variant genotype of ADRA2A rs553668 gene polymorphism had newborns with a higher BW (p = 0.030). MWG and gestational age (GesAge) influenced BW (p < 0.05). We noticed that newborns’ variant genotype of MMP9 rs17577 was related to a significant increase in BW (p = 0.010), while the newborns who carried the variant genotype of MMP9 rs17576 expressed a negative correlation, decreasing the BW (p = 0.032).ConclusionOur study emphasizes the role of MMP9 rs17577, MMP9 rs17576, and ADRA2A rs553668 SNPs in BW determinism.

Polymorphisms in gene MMP-2 modify the association of cadmium exposure with hypertension risk

BackgroundCadmium exposure has been inconsistently related with hypertension. However, epidemiologic data on the genetic susceptibility to the hypertensive effect of cadmium exposure are limited. ObjectivesWe investigated whether the associations between cadmium exposure and hypertension risk differed by genetic polymorphisms in MMPs genes. MethodsThe present study of 497 hypertension cases and 497 healthy controls was conducted in a Chinese population. Urinary cadmium levels were measured with inductively coupled plasma-mass spectrometer (ICP-MS). Multivariable logistic regression models were analyzed after controlling major confounders. ResultsWithin the multivariable logistic regression models, compared with the lowest tertile, the highest tertile of urinary cadmium had a 1.33-fold (95% CI: 1.01, 1.93) increased risk of hypertension. Carriers of rs243865 T allele and rs243866 A allele in MMP-2 were suggested to have increased risks of hypertension. The associations of urinary cadmium with hypertension risk were modified by rs14070 (P-value for interaction = 0.022) and rs7201 (P-value for interaction = 0.009) in gene MMP-2. Positively significant trends for increasing odds of hypertension with cadmium levels were observed among the wild types of rs14070 and rs7201, respectively. ConclusionsIncreasing urinary cadmium concentrations were positively associated with hypertension risk in a Chinese population, and the associations were modified by polymorphism of rs14070 and rs7201 in gene MMP-2.

Association of matrix metalloproteinase 2 and matrix metalloproteinase 9 gene polymorphism in aggressive and nonaggressive odontogenic lesions: A pilot study.

Context:The exact factors that determine the biological behavior of odontogenic lesions have not been thoroughly established yet. The influence of the matrix metalloproteinases (MMPs) on the clinical behavior of these lesions was recently brought to light.Aims:We did a pioneer study to investigate the association of MMP9 (rs3918242 [−1562 C/T] and rs17576) and MMP2 (rs243865 [−1306 C/T] and rs865094) gene polymorphisms and aggressiveness of ameloblastomas, keratocystic odontogenic tumors (KCOT) and dentigerous cysts (DC).Settings and Design:A case–control study conducted in the Department of Oral Pathology and Microbiology, Government Dental College, Trivandrum and Human Molecular Genetics Laboratory, Rajiv Gandhi Institute of Biotechnology and Poojappura, Trivandrum, Kerala.Subjects and Methods:DNA from the blood samples of histopathologically proven ameloblastoma (n = 15), KCOT (n = 11) and DC (n = 13) patients were extracted using standard protocols. Primers were designed based on the functionality and relevance for polymerase chain reaction (PCR). PCR products were analyzed by PCR-restriction fragment length polymorphism and sequencing.Statistical Analysis Used:Chi-square analysis was done to assess the association of gene polymorphisms among the cases and controls.Results:Ameloblastomas showed a higher frequency of mutant allele (T = 0.43; P = 0.05) of MMP9 rs3918242 (−1562C/T) compared to the control population. All the cases showed a statistically significant difference in the distribution of genotype (P = 0.046) and allele (P = 0.03; odds ratio [OR] = 2.06 [1.08–3.95]) frequency of MMP2 rs2438659 (−1306C/T). KCOT samples also showed a significant association in distribution of both genotype (P = 0.01) and allele (P = 0.01 with an OR at 3.42 [1.31–8.92]) frequency, on comparison with control population.Conclusions:MMP2 rs243865 polymorphism has a plausible role in increasing the aggressiveness of ameloblastomas and KCOT compared to that of the control population. Furthermore, MMP9 rs3918242 polymorphism may contribute to the aggressive behavior of ameloblastomas.

Evaluation of genetic polymorphisms in MMP2, MMP9 and MMP20 in Brazilian children with dental fluorosis

Recent studies suggested that genetics contribute to differences in dental fluorosis (DF) susceptibility among individuals having the same environmental exposure. This study evaluated if MMP2, MMP9 and MMP20 are expressed during enamel development and assessed the association between polymorphisms in these genes with DF. Mice susceptible and resistant to DF were used to evaluate if MMPs were candidate genes for DF. The animals received fluoride and their enamels were used for immunohistochemistry. Additionally, 481 subjects from a city with fluoridation of public water supplies were recruited. Genotyping was performed using real time PCR. Allele/genotype frequencies were compared between groups. MMP2, MMP9 and MMP20 immunostaining was detected in both animal groups. DF was observed in 22.4% of the subjects. A borderline association was observed in MMP2 (rs243865), MMP9 (rs17576) and in MMP20 (rs1784418) (p = 0.06, p = 0.08 and p = 0.06 respectively). Briefly, MMPs were expressed during enamel maturation and genetic polymorphisms were not associated with DF.

Role of Polymorphisms in Mmp-9 and Timp-1 As Biomarkers for Susceptibility to Systemic Lupus Erythematosus Patients

To investigate the possible association between MMP-9 (-1562 C/T) and TIMP-1 (372 T/C) polymorphism and inflammatory markers with disease activity in systemic lupus erythematosus (SLE) patients. 150 SLE patients were recruited. Disease severity was assessed by SLEDAI (SLE disease activity index). The polymorphisms were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and serum levels by ELISA. Among patients mean MMP-9 serum levels and mRNA expression were significantly decreased with increase in TIMP-1 levels (p <0.0001). Concomitant presence of both MMP-9 1562 T and TIMP-1 372 C alleles synergistically increased risk of SLE by 7.89-fold (p <0.0001). The mRNA expression of MMP-9 and TIMP-1 correlated with SLEDAI score. MMP-9, TIMP-1 and MMP-9/TIMP-1 ratios may act as biomarkers for susceptibility to SLE.

Impact of Matrix Metalloproteinase 9 on COPD Development in Polish Patients: Genetic Polymorphism, Protein Level, and Their Relationship with Lung Function.

Chronic obstructive pulmonary disease (COPD) is characterized by a decline of lung function and symptoms such as chronic bronchitis and emphysema leading from lung tissue destruction. Increased activity of matrix metalloproteinases (MMPs) and an imbalance between MMPs and their tissue inhibitors (TIMPs) are considered as factors influencing the pathogenesis of COPD. We investigated the role of genetic polymorphism and expression level of MMP-9 and concentration of its complexes with TIMPs in the development of COPD among Polish patients. We analyzed SNP in the promoter region of MMP-9 gene (rs3918242) using PCR-RFLP method among 335 COPD patients and 309 healthy individuals. Additionally, 60 COPD patients and 61 controls were tested for copy number variants (CNV) of MMP-9 (by quantitative real-time PCR) and serum levels of MMP-9 and its complexes with TIMP1 and TIMP2 (using ELISA). All subjects were analyzed for lung function using spirometry (FEV1% and FEV1/FVC parameters). We observed that allele and genotype frequencies of the SNP rs3918242, as well as the number of gene copies, were similar in COPD patient and controls groups. Serum levels of MMP-9 and MMP-9/TIMP1 complex were significantly higher in COPD patients in comparison to controls groups, although independently of analyzed gene polymorphisms. Additionally, the significant inverse relationships between parameters of lung function (FEV1% and FEV1/FVC) and proteins level were found in ridge regression models, especially we found that FEV1% decreased when MMP-9 level increased in controls and patients with COPD group. In conclusion, we found that COPD patients were predisposed to produce more MMP-9 and MMP-9/TIMP1 complex than healthy individuals. This phenomenon is probably associated with the disease-related lung environment but not with genetic features of the MMP-9.

Matrix Metalloproteinase-2 Single Nucleotide Polymorphism in Egyptian Non-Hodgkin Lymphoma Patients: Correlation with Clinicopathological Characteristics and Outcome.

Non-Hodgkin's lymphoma (NHL) is an exceedingly diversified group of lymphoproliferative neoplasms emerging from B-, T- or natural killer -lymphocytes. This study was done to detect Matrix metalloproteinase-2 (MMP2)-735C/T gene polymorphism in patients with NHL and its relation to the clinicopathological characteristics of the studied patients in addition to detection the association between it and NHL disease susceptibility and progression. Clinico-hematological profiles were done on 50 NHL patients. The genotypes and allelic frequencies of MMP-2 polymorphisms were recognized utilizing Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP). PCR products after adding restriction endonuclease were analyzed using QIAxcel advanced (automated) instrument. The CT + TT genotypes and T allele of MMP2 735C/T were statistically significant in patients having advanced clinical stages III/IV compared to patients with stages I/II. Another significance was observed in patients with intermediate high/high IPI score and BM infiltration. Interestingly, patients with MMP2-735C/T genotype exhibit lower rate of survival. Our results demonstrated that MMP2-735C/T polymorphism may potentially affect the progression of NHL. Further larger scale studies are needed.

Polymorphism of MMP-9 gene is not associated with the risk of urinary cancers: Evidence from an updated meta-analysis

ObjectiveMatrix metalloproteinases 9 (MMP-9) is a zinc-dependent gelatinase, which could decrease the expression of extracellular matrix proteins and influence the metastatic behavior of tumors. In order to draw a comprehensive and precise result about the relationship of MMP-9 and urinary cancers, we presented the current meta-analysis. MethodsWe searched the PubMed, EMbase, Web of Science, CBM, CNKI and Wanfang databases, the cited references were also manually searched again, covering all the papers published until August 2018. Quality assessment was conducted using the Newcastle–Ottawa Scale. All the meta-analysis was conducted with Stata version 12.0 software to assess the strength of the association. Linkage disequilibrium (LD) analyses of gene polymorphisms and in-silico analysis of MMP-9 expression were also conducted to illustrate the relationship. Results17 case-control studies comprise of more than 6154 cases and 6330 controls were enrolled and analyzed. After analyzed, we found that there is no significant association between rs3918241, rs2250889, rs17576 and rs17577 of MMP-9 and urinary cancers. LD analysis uncovered a significant LD between rs3918241 and rs17577 in CEU, CHB&CHS, ESN, and JPT populations (CEU: r2 = 1.0; CHB&CHS: r2 = 1.0; ESN: r2 = 0.74; JPT: r2 = 0.77), as well as a remarkable LD between rs17576 and rs2250889 in CHB&CHS and JPT populations (CHB&CHS: r2 = 0.81; JPT: r2 = 0.82). Furthermore, in-silico results indicated that the expression of MMP-9 in cancer tissue was higher than that in normal tissue in prostate cancer (Transcripts Per Kilobase Million (TPM) = 7.14 vs. 1.36, P < 0.001), bladder cancer (TPM = 14.2 vs. 2.47, P < 0.001), kidney renal clear cell carcinoma (TPM = 7.43 vs. 1.61, P < 0.001), kidney renal papillary cell carcinoma (TPM = 5.52 vs. 1.74, P = 0.002). Conclusionsrs3918241, rs2250889, rs17576 and rs17577 polymorphisms of MMP-9 are not associated with altered risk of urinary cancer. More studies with large sample size focused on the combined effect of two or more polymorphisms of MMP-9 are necessary in the future.

MMP8 and MMP9 gene polymorphisms were associated with breast cancer risk in a Chinese Han population

Matrix metalloproteinases (MMPs) are a group of zinc-dependent endopeptidases that can breakdown almost all extracellular matrix components. MMP8 and MMP9 have been shown to be associated with breast cancer (BC) risk in European and American populations. However, few studies have focused on the polymorphisms of MMP8 and MMP9 in Chinese Han BC patients. We investigated nine single nucleotide polymorphisms (SNPs) in 571 BC cases and 578 controls to evaluating their association with risk of BC. The frequency of the “A” allele of rs3787268 was significantly lower in BC cases than in controls (P = 0.025). In the genetic model analysis, the minor allele “T” of rs11225394 in MMP8 was associated with increased risk of BC under the recessive model (P = 0.019), and the minor allele “A” of rs3787268 was associated with decreased risk of BC under the dominant model (P = 0.014). Additionally, the haplotype “AGTCA” constructed by rs3740938, rs2012390, rs1940475, rs11225394, and rs11225395 and the haplotype “CCG” constructed by rs3918249, rs3918254 and rs3787268 were associated with increased risk of BC (P < 0.05). Our data showed that polymorphisms of MMP8 and MMP9 may be associated with BC risk in the Chinese Han population.