Matrix Metalloproteinase Gene Polymorphisms Research Articles

Matrix metalloproteinase-9 gene polymorphisms and their interaction with environment on subarachnoid hemorrhage risk.

The current study aimed to investigate the relations of three single nucleotide polymorphisms of matrix metalloproteinase-9 gene, and single nucleotide polymorphisms-smoking interaction to subarachnoid hemorrhage risk. The optimal pattern of the interaction among single nucleotide polymorphisms and smoking was selected by generalized multifactor dimensionality reduction. The association between the three single nucleotide polymorphisms within the matrix metalloproteinase-9 gene was analyzed by logistic regression test. As well as genetic risk of subarachnoid hemorrhage interactions with smoking, the risk of subarachnoid hemorrhage in carriers with the rs3918242 (T) was significantly higher than in carriers carrying CC (genotype: CT + TT vs. CC), adjusted OR (95% CI) = 1.58 (1.25-2.03), and in carriers carrying rs17576- (genotype: AG + GG vs. AA), adjust OR (95% CI) = 1.62 (1.19-2.13). However, after adjusting for covariates, we did not find any direct association between rs17577 and subarachnoid hemorrhage risk. The generalized multifactor dimensionality reduction model shows a potential relation between rs3918242 and smoking risk for subarachnoid hemorrhage ( P = 0.0010). After covariates adjustment, current smokers with rs3918242-CT or TT genotype, compared to never-smokers with rs3918242-CC genotype, OR (95% CI) = 2.57 (1.74-3.46), have a higher subarachnoid hemorrhage risk. Our study showed that the rs3918242 (T) and rs17576 (G), the cross reaction between rs3918242 and smoking increased the risk of subarachnoid hemorrhage. Impact statement Matrix metalloproteinase-9 ( MMP-9) is a possible candidate gene for some diseases, including metabolic syndrome, stroke, coronary artery disease (CAD). But to date, limited data focused on the relationship between MMP-9 gene SNPs and SAH susceptibility. The purpose of this study was to evaluate SNPs of MMP-9 gene and their interaction with environmental factors with SAH risk based on a Chinese population.

The Relationship between Matrix Metalloproteinase Gene Polymorphisms and Tumor Type, Tumor Size, and Metastasis in Women with Breast Cancer in Central Iran

Background: Matrix metalloproteinases-2 and -9 play important roles in the development of breast cancer by hydrolyzing the extracellular matrix. Since −1306C/T and −1562C/T polymorphisms are located at the promoter regions of the matrix metalloproteinase- 2 and -9 genes, respectively, C to T substitution may affect promoter activity and impact the rate of extracellular matrix degradation and cancerous cell proliferation. Therefore, we aimed to determine the genotype and allele frequencies of these polymorphisms in Iranian healthy women and women with breast cancer. We have also examined the correlation of genotypes with clinicopathological parameters such as tumor type, tumor size, and metastasis to lymph nodes. Methods: This case-control study enrolled 200 women with breast cancer and 200 age-matched healthy women. DNA was extracted, and we determined the genotype and allele frequencies of −1306C/T matrix metalloproteinase-2 and −1562C/T matrix metalloproteinase-9 polymorphisms by the polymerase chain reaction-restriction fragment length polymorphism method. Additionally, tumor size (20 mm), tumor type (ductal/non-ductal), and metastasis (yes/no) were determined. Results: Genotype and allele frequencies of the −1306C/T matrix metalloproteinase- 2 polymorphism showed no significant association with the occurrence of breast cancer. Genotype and allele distribution differed in the −1562C/T matrix metalloproteinase- 9 polymorphism and indicated a 4.83-fold increase in the risk of breast cancer for T allele carriers. There was no likelihood of any interaction found between the two polymorphisms and susceptibility to breast cancer. In addition, the −1562C/T matrix metalloproteinase-9 T allele showed an association with metastasis to lymph nodes but we observed no association between the −1306C/T matrix metalloproteinase- 2 polymorphism and clinicopathological features. Conclusion: The ‒1562C/T matrix metalloproteinase-9 polymorphism is involved in the pathogenesis of breast cancer in Iranian women. The T allele may increase the risk of disease.

Matrix metalloproteinase and tissue inhibitors of metalloproteinases gene polymorphisms in disorders that influence fertility and pregnancy complications: A systematic review and meta-analysis

Matrix metalloproteinase (MMP) and tissue inhibitors of metalloproteinase (TIMP) gene polymorphisms have been extensively evaluated as predisposing factors to human reproductive disorders. However, the evidence available is inconsistent. Therefore, we performed a systematic review and meta-analysis to provide the first comprehensive synopsis of case-control studies that investigated the association of MMP and TIMP gene polymorphisms with disorders that influence fertility and pregnancy complications. Literature search was performed using PubMed and Scopus databases. We included 42 case-control studies in the systematic review for the following disorders: adenomyosis, endometriosis, hypertensive disorders of pregnancy, preterm birth and recurrent spontaneous abortion. Although a large number of MMP and TIMP gene polymorphisms were tested, no exclusive and unambiguous risk factors were identified for any of the disorders. The majority of statistically significant associations were confirmed in just one study. Additionally, we performed two meta-analyses for MMP9 rs3918242 polymorphism in endometriosis/adenomyosis and preeclampsia but found no association with either disorder. Considering the modest associations and conflicting results between individual case-control studies, new data is needed for further research of this subject.

Association of Polymorphisms of the Matrix Metalloproteinase 9 Gene with Ischaemic Stroke in a Southern Chinese Population

Background/Aims: Matrix metalloproteinase 9 (MMP9), a potent endopeptidase degrading extracellular matrix, plays a pivotal role in the pathogenesis of ischaemic stroke (IS). The present study was undertaken to determine the association of MMP9 gene polymorphisms and the risk of IS in a southern Chinese population. Methods: A cohort of 1274 patients and 1258 age-matched healthy controls were genotyped to detect the four MMP9 polymorphisms (rs17156, rs3787268, rs3918241 and rs3918242) using SNaPshot. Results: Our study demonstrated a significant difference in the genotype and allele frequencies of the MMP9 rs3918242 polymorphism between the IS patients and the controls (P = 0.012 for the genotype and P = 0.0092 for the allele). Stratification by smoking status showed statistically significant differences in the frequency and allele of the rs3918242 polymorphism between IS patients and the controls (P = 0.0052 for the genotype and P = 0.0019 for the allele). Further stratification by IS subtypes revealed that the presence of the T allele of the MMP9 rs3918242 polymorphism confers a higher risk of the large artery atherosclerosis subtype of IS (P = 0.017). Moreover, IS patients with the rs3918242 T allele of MMP9 presented with increased serum MMP9 production, and this increase was more significant in smokers with IS (P = 0.022). Patients carrying the variant T allele of the MMP9 rs3918242 polymorphism exhibited significantly higher infarct volumes than those with the major CC genotype (P = 0.036). Conclusion: Our study provides preliminary evidence that the MMP9 rs3918242 polymorphism is linked to a higher risk of IS, confirming the role of MMP9 in the pathophysiology of IS, with potentially important therapeutic implications.

No Association of Genetic Markers with Carotid Intimal Medial Thickness in β-Thalassemia Major Patients

Regular transfusion leads to cardiac siderosis resulting in cardiac complications that account for more than 71% of the total mortality in thalassemia patients. We aimed to study the variants of matrix metalloproteinase-9 (MMP9), matrix Gla protein (MGP), and estrogen receptor α(ERα), which might be contributing to atherosclerosis, leading to heart failure in thalassemia major. One hundred and five thalassemia patients on regular transfusion and iron chelation therapy were enrolled for the study. Carotid artery intimal medial thickness (CIMT) measurement was done to check for atherosclerosis. MMP 9 (C1562T), MGP (T138C), and ER α gene ( Pvu II (rs2234693T > C) and Xba I (rs9340799A > G) polymorphism were analyzed using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. CIMT values were within the normal range (<0.90 mm) in all patients. There was no difference in mean CIMT values between males and females (0.56 ± 0.11 versus 0.56 ± 0.12, p = 0.928). There was no correlation of CIMT with age, body surface area, and body mass index as well as with serum ferritin levels. No statistically significant difference in frequency of MMP9, MGP, and ERα genotypes was seen in two dichotomized groups of CIMT (CIMT < 0.56 and CIMT ≥ 0.56). Variants of MMP9 , MGP , and ERα have a reserved influence on cardiac disease pathogenesis, and the disease phenotype in thalassemia patients may be more strongly impacted by other factors.

Genetic Association between Matrix Metalloproteinases Gene Polymorphisms and Risk of Prostate Cancer: A Meta-Analysis.

Background and Objective: Studies suggests that matrix metalloproteinase (MMP)-2-1306 C/T and MMP-1-1607 1G/2G polymorphisms affect the risk of prostate cancer. However, the conclusions remain controversial and no pooled evidence of this topic has been published. Therefore, we aimed to perform a meta-analysis to shed some light on the controversial conclusion pertaining to the associations of MMP-2-1306 C/T and MMP-1-1607 1G/2G polymorphisms with prostate cancer susceptibility.Methods: A thorough literature search was performed up to August, 2016 with the PubMed, EMBASE, CBM, CNKI, and Wanfang databases. Odds ratios (ORs) and corresponding 95% confidence intervals (95% CIs) were calculated to address the correlations between these polymorphisms and risk of prostate cancer.Results: The meta-analysis included six studies (1,921 patients and 1,988 controls) on MMP-2-1306 C/T polymorphism and three studies on MMP-1-1607 1G/2G polymorphism (438 patients and 394 controls), respectively. The overall results of meta-analysis showed that an elevated risk of the disease was implicated in MMP-2-1306 C/T polymorphism under two genetic models (CT vs. CC: OR = 1.78, 95% CI = 1.33–2.38; TT+CT vs. CC: OR = 1.62, 95% CI = 1.24–2.12) and no significant association was observed between MMP-1-1607 1G/2G polymorphism and the risk of prostate cancer. The subgroup analysis results of MMP-2-1306 C/T polymorphism were similar to the overall results. However, decreased risk of prostate cancer was observed in the Caucasians for MMP-1-1607 1G/2G polymorphism.Conclusions: Current meta-analysis indicates that MMP-2-1306 C/T polymorphism is associated with elevated risk of prostate cancer, but MMP-1-1607 1G/2G polymorphism may inhibit the occurrence of prostate cancer in Caucasians. Further studies are warranted to verify the conclusions.

Matrix Metalloproteinase Gene Polymorphisms in Periodontitis in Taiwanese Population

Matrix Metalloproteinase Gene Polymorphisms in Periodontitis in Taiwanese Population

Analysis of MMP-3 polymorphism in osseointegrated implant failure

Polymorphisms in matrix metalloproteinases (MMPs) genes have been associated with several pathologies, including dental implant loss. MMP-3 is crucial to the connective tissue remodeling process. The objective of this study was to investigate the possible relationship between -1612 MMP-3 polymorphism and the early implant failure. A sample of 240 non-smokers was divided: test group 120 patients with one or more early failed implants and control group 120 patients with one or more healthy implants. Genomic DNA from oral mucosa was analyzed by PCR-RFLP. No association of early implant loss with genotypes and alleles of the -1612 polymorphism in MMP-3 were found by the Chi-squared test. Only the presence of the -1612 polymorphism of MMP-3 is not a genetic risk factor for early loss of implants.

Association of R279Q and C1562T polymorphisms of matrix metalloproteinase 9 gene and increased risk for myocardial infarction in patients with premature coronary artery disease.

A number of matrix metalloproteinase (MMP) gene polymorphisms has been identified which may be probably related to premature myocardial infarction (MI). We assessed the relationship between the two polymorphisms of the MMP9 gene including R279Q and C1562T and occurrence of premature MI. The study has two phases including a case-control study as the first phase and cohort study as the second phase. Initially, 1000 patients with premature coronary artery disease were classified into MI and non-MI groups. Genotyping of the polymorphism was conducted by PCRRFLP and high-resolution melting techniques. Given the two conditions of patients residing in Tehran and faced with their first episode of MI, 640 of 1000 study samples previously followed up with a median follow-up time of 45.74months were assessed in a retrospective cohort phase regarding long-term major adverse cardiac events (MACE). The prevalence of wild, heterozygous, and mutant genotypes of R279Q polymorphism in MI group was 14.5%, 57.3%, and 28.2% and in non-MI group was 36.9%, 38.4%, and 24.7%, respectively, with a considerable difference (P<.001). There was a significant difference in the prevalence of wild, heterozygous, and mutant genotypes of C1562T polymorphisms in MI group (12.4%, 41.2%, and 46.4%, respectively) and in non-MI group (46.8%, 38.6%, and 14.7%, respectively; P<.001). No difference was found in total MACE-free survival rate between genotypes of R279Q and C1562T polymorphisms. C1562T and R279Q polymorphisms are associated with the susceptibility to premature MI, but cannot predict long-term cardiac events in these patients.

Associations between matrix metalloproteinase gene polymorphisms and glaucoma susceptibility: a meta-analysis

BackgroundMatrix metalloproteinases (MMPs) polymorphisms have been implicated in the pathogenesis of glaucoma risk. However, the results were controversial. We performed a meta-analysis to evaluate the precise associations between MMPs polymorphisms and glaucoma risk.MethodsRelated studies were reviewed by searching electronic databases within four databases. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to assess the association between the most common polymorphisms of MMPs and glaucoma risk. Heterogeneity, publication bias and sensitivity analysis were conducted to guarantee the statistical power.ResultsOverall, 11 selected articles involving 2,388 cases and 2,319 controls were included in this meta-analysis. Significant associations were only found between MMP-9 rs17576 G > A polymorphism (GA vs. GG: OR = 0.80, 95%CI = 0.67-0.97, P = 0.02, I2 = 0%), MMP-9 rs3918249 C > T polymorphism (TT vs. CC + CT: OR = 0.71, 95%CI = 0.51-0.98, P = 0.04, I2 = 0%) and glaucoma risk in the general population. Subgroup analysis also suggested that MMP-9 rs17576 G > A was related to glaucoma in the Caucasian population (GA vs. GG: OR = 0.67, 95%CI = 0.45-1.00, P = 0.05; GA + AA vs. GG: OR = 0.66, 95%CI = 0.45-0.97, P = 0.03, I2 = 0%).ConclusionsOur meta-analysis demonstrates that MMP-9 rs17576 G > A polymorphism might be a protective factor against the development of glaucoma in Caucasian population.

Matrix metalloproteinase-9 gene polymorphisms and the risk for oral squamous cell carcinoma metastasis

Matrix metalloproteinase-9 gene polymorphisms and the risk for oral squamous cell carcinoma metastasis

Alliance of matrix metalloproteinase-9 (MMP-9) promoter gene polymorphism with chronic and aggressive periodontitis in Indian population

BackgroundMatrix metallo proteinases (MMPs) are associated with tissue destruction and remodeling occurrence in chronic periodontitis. In this literature we performed a case-control study to investigate a possible association of single nucleotide polymorphism of MMP-9 with aggressive and chronic periodontitis in Indian population. MethodsA total of 269 DNA samples from venous blood have been isolated, 110 identified chronic periodontitis (CP) patients, 38 Aggressive periodontitis (AgP) patients and 121 healthy individuals. The MMP-9 gene (rs3918242) has a functional single nucleotide polymorphism −1562C/T in the promoter region. RFLP (restriction fragment length polymorphism) analysis was performed followed by PCR (polymerase chain reaction) by using SphI restriction enzyme. Allele frequency and epidemiological effects were calculated and analyzed by chi square test and logistic regression. ResultsThe distribution of MMP9 −1562C/T genotypes and alleles were significantly different between disease groups and control group. T allele carriage is higher in both AgP and CP group compared to control group. Regression analysis showed significant association of T allele carriage in AgP (OR=3.762, 95% CI=1.47–9.66, p=0.006) however in CP group this T allele carriage did not show any association. ConclusionThe findings suggest that the genetic polymorphism of MMP-9 gene is associated with the increased susceptibility to aggressive periodontitis as well as to chronic periodontitis among Indian population.

Matrix Metalloproteinase-9 and Synaptic Plasticity in the Central Amygdala in Control of Alcohol-Seeking Behavior

BackgroundDysfunction of the glutamatergic system has been implicated in alcohol addiction; however, the molecular underpinnings of this phenomenon are still poorly understood. In the current study we have investigated the possible function of matrix metalloproteinase-9 (MMP-9) in alcohol addiction because this protein has recently emerged as an important regulator of excitatory synaptic plasticity. MethodsFor long-term studies of alcohol drinking in mice we used IntelliCages. Dendritic spines were analyzed using Diolistic staining with DiI. Whole-cell patch clamp was used to assess silent synapses. Motivation for alcohol in human subjects was assessed on the basis of a Semi-Structured Assessment for the Genetics of Alcoholism interview. ResultsMice devoid of MMP-9 (MMP-9 knockout) drank as much alcohol as wild-type animals; however, they were impaired in alcohol seeking during the motivation test and withdrawal. The deficit could be rescued by overexpression of exogenous MMP-9 in the central nucleus of the amygdala (CeA). Furthermore, the impaired alcohol seeking was associated with structural alterations of dendritic spines in the CeA and, moreover, whole-cell patch clamp analysis of the basal amygdala to CeA projections showed that alcohol consumption and withdrawal were associated with generation of silent synapses. These plastic changes were impaired in MMP-9 knockout mice. Finally, C/T polymorphism of MMP-9 gene at position –1562, which upregulates MMP-9 expression, correlated with increased motivation for alcohol in alcoholics. ConclusionsIn aggregate, our results indicate a novel mechanism of alcohol craving that involves MMP-9–dependent synaptic plasticity in CeA.

Plasma concentration, genetic variation, and gene expression levels of matrix metalloproteinase 9 in Iranian patients with coronary artery disease

Background:Matrix metalloproteinase 9 (MMP9) -1562C>T (rs3918242) polymorphism has been proposed as a risk factor for coronary artery disease (CAD) with conflicting results. The aim of the present study was to investigate the association of -1562C>T genetic polymorphism, gene expression and circulating levels of MMP9 with CAD risk in an Iranian subpopulation in in Zanjan City.Materials and Methods:This was a retrospective case–control study we investigated retrospectively 100 patients with angiographically verified CAD and 100 matched controls. Genotyping of -1562C>T polymorphism was done by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Gene expression levels and circulating levels of MMP9 was determined by real-time reverse transcription-PCR and enzyme immunoassay method, respectively. Statistical analysis was done using Student's t-test or Chi-square test by SPSS 16 software.Results:The mean circulating levels of MMP9 were significantly higher in CAD Group than control group (P = 0.002). Mean plasma levels of MMP9 were also significantly higher in triple vessel stenosis patients than double vessel or single vessel stenosis patients (P < 0.001). Moreover, mean plasma levels and gene expression levels of MMP9 were significantly higher in T allele carrier than C allele carrier of MMP9 -1562C>T polymorphism (P = 0.002, P = 0.01, respectively). However, genotype and allele frequencies of MMP9 -1562C>T polymorphism were similar between CAD patients and controls (P > 0.05). Additionally, the -1562C>T polymorphism of MMP9 gene didn't increase the risk of CAD in dominant (P = 0.537) or recessive (P = 0.249) genetic models.Conclusion:Our study demonstrated that circulating levels of MMP9 but not -1562C>T polymorphism of MMP9 gene may be a risk factor for development and severity of CAD in an Iranian subpopulation in Zanjan.

Association Study of MMP-9 −1562C/T Gene Polymorphism with Susceptibility to Multiple Autoimmune Diseases: A Meta-analysis

Matrix metalloproteinase-9 (MMP-9) -1562C/T gene polymorphism has been identified as a susceptible gene for multiple autoimmune diseases (ADs), but studies are inconsistent. The aim of this study was to assess the overall association between MMP-9 gene polymorphism and multiple ADs using a meta-analysis. Databases of Pubmed, Embase and Web of Science updated to March 1, 2016 were retrieved. Odds ratios (ORs) and corresponding 95% confidence intervals (95% CIs) as effect size were calculated by fixed-effect or random-effect model on the basis of heterogeneity. A total of 12 relevant studies containing 2,034 cases and 1,861 controls were included in this meta-analysis. A significant association between MMP-9 -1562T allele and AD susceptibility was found in the overall population (OR=1.269, 95% CI=1.114-1.444, p <0.001) and the Caucasian populations (OR=1.222, 95% CI=1.051-1.422, p=0.009), but not in the Asian populations (OR=1.337, 95% CI=0.989-0.808, p=0.059). Stratified by disease type, we detected a significant association in other ADs (OR=1.501, 95% CI=1.212-1.859, p <0.001), but not in patients with multiple sclerosis (OR=1.150, 95% CI=0.977-1.354, p=0.092). No publication bias was detected in the current meta-analysis. Data from the present study suggest that the MMP-9 -1562C/T polymorphism may be associated with multiple AD susceptibility, especially in the Caucasian populations and other ADs. Further epidemiological studies with a larger sample size are needed to confirm these findings.

Polymorphisms in Genes of Cytokines and Matrix Metalloproteinases Associated With Ischemic Heart Disease in Patients With Type 2 Diabetes

To examine associations between ischemic heart disease (IHD) and polymorphisms in cytokine genes (IL-1B, IL-4, IL-6, IL-10, TNFA, VEGF) and matrix metalloproteinase genes (MMP2, MMP3, MMP9) in patients with type 2 diabetes. We studied 232 Caucasian diabetic subjects (33 men and 199 women aged 50-70 years). In 93 patients IHD was verified by treadmill test and/or coronary angiography (86 subjects with stable angina, 19 with previous myocardial infarction). Thirteen polymorphisms localized in the promoters of IL-1B (rs1143627), IL-4 (rs2243250), IL-6 (rs1800795), IL-10 (rs1800872, rs1800896), TNFA (rs361525, rs1800629, rs1800630), VEGF (rs699947, rs3025039), MMP2 (rs243865), MMP3 (rs3025058) and MMP9 (rs3918242) were investigated. Prevalence of G-allele and GG-genotype at -308 position of TNFA (rs1800629), as well as C-allele and CC-genotype at position +936 of VEGF (rs3025039) was higher in patients with IHD as compared to patients without IHD (OR=2.0, OR=2.2, OR=2.1, OR=2.4, respectively, all p=0.02). In logistic regression analysis, TNFA -308 A/G and VEGF +936 C/T polymorphisms showed associations with IHD (both p=0.009). These polymorphisms along with age, body mass index, duration of diabetes, low density and high density lipoprotein cholesterol were associated with IHD in multivariate models (p=0.0002 and p=0.00008, respectively). Nine combinations of TNFA -308 GG-genotype and variants of other genes demonstrated associations with IHD (p≤0.002). The polymorphisms in promoter regions of TNFA (rs1800629) and VEGF (rs3025039) are associated with IHD in patients with type 2 diabetes.

The Role of Matrix Metalloproteinase Polymorphisms in Ischemic Stroke

Stroke remains the fifth leading cause of mortality in the United States with an annual rate of over 128,000 deaths per year. Differences in incidence, pathogenesis, and clinical outcome have long been noted when comparing ischemic stroke among different ethnicities. The observation that racial disparities exist in clinical outcomes after stroke has resulted in genetic studies focusing on specific polymorphisms. Some studies have focused on matrix metalloproteinases (MMPs). MMPs are a ubiquitous group of proteins with extensive roles that include extracellular matrix remodeling and blood-brain barrier disruption. MMPs play an important role in ischemic stroke pathophysiology and clinical outcome. This review will evaluate the evidence for associations between polymorphisms in MMP-1, 2, 3, 9, and 12 with ischemic stroke incidence, pathophysiology, and clinical outcome. The role of polymorphisms in MMP genes may influence the presentation of ischemic stroke and be influenced by racial and ethnic background. However, contradictory evidence for the role of MMP polymorphisms does exist in the literature, and further studies will be necessary to consolidate our understanding of these multi-faceted proteins.

MMP3 -1171 5A/6A Promoter Genotype Influences Serum MMP3 Levels and Is Associated with Deep Venous Thrombosis

The aim of this study was to investigate the roles of MMP3 (matrix metalloproteinase-3) gene polymorphism and protein expression in deep venous thrombosis (DVT) among Chinese Han population. A total of 280 subjects were included in this study and categorized as case group (144 DVT patients) and control group (136 healthy individuals). Polymerase chain reaction-restriction fragment length polymorphism was used to detect MMP3 promoter -1171 5A>6A genotype and allele frequencies. MMP3 serum levels were measured by enzyme-linked immunosorbent assay. SPSS version 18.0 statistical software was used for data analysis. There was significant difference in genotype frequencies of MMP3 gene -1171 5A>6A between the case group and the control group (all P<0.05). Furthermore, the 6A allele on MMP3 -1171 5A>6A may be associated with increased risk of DVT (odds ratio 1.961, 95% confidence interval 1.309-2.939, P<0.01). The MMP3 serum level in DVT patients was markedly higher than the control group (case group: 28.45 ± 10.97 vs. 18.18 ± 9.03, P<0.05). Serum MMP3 level in DVT patients carrying 5A/6A and 6A/6A genotypes was higher than the control group (P<0.05). The bilateral calf circumference difference was significantly higher in DVT patients than the control group among all the genotypes at MMP3 gene -1171 5A>6A (all P<0.05). MMP3 gene -1171 5A>6A polymorphism and upregulated protein expression may be associated with DVT risk in Chinese Han population.

Matrix Metalloproteinase Gene Polymorphisms and New-Onset Diabetes After Kidney Transplantation in Korean Renal Transplant Subjects

BackgroundNew-onset diabetes after transplantation (NODAT) is a serious metabolic complication that may follow renal transplantation. Matrix metalloproteinases (MMPs) contribute to insulin insufficiency and beta-cell dysfunction in a rat model. The MMP-2 concentrations were lower in patients with type 2 diabetes mellitus, and the plasma MMPs levels were related to diabetes. Similar to the pathogenesis of type 2 diabetes mellitus, insulin resistance and insulin secretion dysfunction occur in patients with the development of NODAT. Therefore, we examined the association between NODAT and 11 single-nucleotide polymorphisms (SNPs) located within the 3 genes of MMPs that might be related to NODAT. MethodsA total of 309 renal transplant recipients without a history of diabetes were included in this study. DNA was extracted from the blood samples of recipients, and we analyzed the association between the development of NODAT and a panel of 11 SNPs within 3 MMP genes (MMP-1, MMP-2, and MMP-3). ResultsIn terms of allele frequencies, rs243849*C (MMP-2) was significantly higher in patients with NODAT. Two of the 11 (18.1%) SNPs were significantly associated with NODAT development after adjusting for age, sex, and tacrolimus usage: MMP-2 (rs1132896) and MMP-2 (rs243849). In the multiple logistic regression analysis, these 2 SNPs were significantly associated with the development of NODAT in the codominant and recessive or codominant and dominant models. ConclusionsMMP-2 gene rs1132896 and rs243849 polymorphisms may serve as genetic markers for the development of NODAT. The exact molecular mechanisms still must be clarified.

Matrix metalloproteinase gene polymorphisms and periodontitis susceptibility: a meta-analysis involving 6,162 individuals.

We aimed to systematically investigate the potential association of matrix metalloproteinase (MMP)-9, -3, -2, and -8 gene polymorphisms with susceptibility to periodontitis using meta-analysis. A literature search in PubMed, Embase, and Web of Sciencewas conducted to obtain relevant publications. Finally a total of 16 articles with 24 case-control studies (nine on MMP-9-1562 C/T, seven on MMP-3-1171 A5/A6, four on MMP-2-753C/T, and four on MMP-8-799 C/T) were considered in this meta-analysis. The results based on 2,724 periodontitis patients and 3,438 controls showed that MMP-9-1562C/T, MMP-3-1171 A5/A6, and MMP-8-799C/T polymorphisms were associated with periodontitis susceptibility. No significant association was found between MMP-2-753 C/T and periodontitis susceptibility. Subgroup analyses suggested that the MMP-9-1562 C/T polymorphism reduced chronic periodontitis susceptibility and MMP-3-1171 A5/A6polymorphism increased chronic periodontitis susceptibility. In summary, current evidence demonstrated that MMP-9-753 C/Tpolymorphism reduced the risk of periodontitis, MMP-3-1171 5A/6A and MMP-8-799 C/Tpolymorphisms increased the risk of periodontitis, and MMP-2-753 C/T was not associated with risk of periodontitis.