Matrix Metalloproteinases Polymorphisms Research Articles

Current evidence on the relationships among five polymorphisms in the matrix metalloproteinases genes and prostate cancer risk.

Matrix metalloproteinases (MMPs) had a variety of subtypes, which may be related to tumor invasion and angiogenesis, and the polymorphisms from MMPs have been also associated with the susceptibility to a variety of tumors, including prostate cancer (PCa). However, previous studies have not systematically analyzed the association between MMP and prostate cancer, so we conducted systematic data collection and analyzed to evaluate the relationship among polymorphisms in MMPs and PCa susceptibility. We searched PubMed, Web of Science, Embase and Google Scholar for all papers published up to Apr 3rd, 2023, and systematically analyzed the relationship among MMP1-1607 2G/1G, MMP2-1306T/C, MMP2-735T/C, MMP7-181 G/A, MMP9-1562T/C and PCa susceptibility using multiple comparative models and subgroup analyses. We found that MMP2-1306T/C polymorphism showed associations with PCa susceptibility, with the Ethnicity subgroup (Asian) being more pronounced. Similarly, MMP9-1562T/C has also had associations with PCa susceptibility. Our current study found that the polymorphisms of, MMP2-1306T/C, and MMP9-1562T/C had strong associations with PCa risk.

The association between genetic polymorphisms of matrix metalloproteinases and knee osteoarthritis: A systematic review and meta-analysis.

To investigate the linkage of matrix metalloproteinase (MMP) gene polymorphisms with the pathogenesis of knee osteoarthritis (OA). This meta-analysis study systematically retrieved relevant studies from PubMed, Embase, the Cochrane Central, Wanfang Data, CNKI, and SinoMed up to November 2020. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to estimate the association between MMP gene polymorphisms and OA. A total of nine case-control studies comprising 1719 knee OA patients and 1904 controls were included in this meta-analysis. The results revealed that MMP-1-1607 (rs1799750) 1G/2G polymorphism was not significantly associated with knee OA risk in four genetic models (OR (95% CI): allele model: 0.89 (0.57, 1.40), p = .615); dominant mode: 0.82 (0.47, 1.44), p = .486; recessive model: 0.88 (0.49, 1.57), p = .659; homozygote model: 0.79 (0.34, 1.82), p = .576. The association was significant for dominant model of MMP-3 C/T: 1.54 (1.10-2.15), p = .013, especially in Asian ethnicity (1.63 (1.11, 2.39), p = .013). Variants of MMP-13 C/T polymorphism were associated with increased risk of knee OA development based on dominant model: 1.56 (1.19, 2.06), p = .001 and homozygote model: 2.12 (1.44, 3.13), p < .001, and there were significant associations between MMP-13 C/T polymorphism and knee OA risk in Asian ethnicity under different genetic models (all p > .05). Present evidence suggested that the gene polymorphisms of MMP-1-1607 1G/2G may not be associated with the risk of OA. But, the dominant model of MMP-3 and MMP-13 polymorphisms in Asian ethnicity was significantly correlated with knee OA.

Potential genetic polymorphism of matrix metalloproteinase (MMP)-9 in Iranian migraine patients with Toxoplasma gondii infection.

Toxoplasma gondii is an intracellular protozoan parasite that causes neuroinflammation in the brain and a constant need for peripheral leukocyte migration. Matrix metalloproteinase 9 (MMP-9) can play a major role in this neuroinflammation and be implicated in some neurological disorders, such as migraines. Therefore, the genetic polymorphism evaluation of MMP-9 in migraine patients with T. gondii infection was performed. One hundred fourteen migraine patients and 114 healthy controls were evaluated for the presence of anti-Toxoplasma IgG antibodies. Seventy-two migraine patients and 40 healthy controls were randomly selected for assessment of the MMP 9-1562C/T genetic polymorphism. In the preliminary examination, 61 (53.5%) migraine patients and 43 (37.3%) healthy controls were positive for IgG antibodies, with a significant association between T. gondii seropositivity and migraine (OR = 1.90; 95% CI = 1.21-3.223; P = 0.012). Genetic distribution for the polymorphism was not in Hardy-Weinberg equilibrium in cases but showed no significant variation in control groups (P = 0.03 and P = 0.180, respectively). A significant preponderance of the CT + TT genotype was found in migraine subjects compared to controls (P = 0.042) (OR, 1.77, CI, 1.013-2.229). The homozygote muted allele TT had a higher rate in migraine patients (6.9%). There were significant differences in CT + TT genotype between T. gondii positive and negative migraine patients (P = 0.024), but T allele frequencies had no significant variation (OR 1.7 CI, 1.084-2.44 and 0.42 CI, 0.044-3.97, respectively). In conclusion, the results may provide the first evidence for the involvement of the MMP-9 gene polymorphism in the mechanism of migraine pathology following Toxoplasma infection.

The multifaceted roles of matrix metalloproteinases in lung cancer.

Though the matrix metalloproteinases (MMPs) are widely investigated in lung cancer (LC), however, almost no review systematically clarify their multi-faced roles in LC. We investigated the expression of MMPs and their effects on survival of patients with LC, the resistance mechanisms of MMPs in anti-tumor therapy, the regulatory networks of MMPs involved, the function of MMPs inducing CSCLs, MMPs-related tumor immunity, and effects of MMP polymorphisms on risk of LC. High expression of MMPs was mainly related to poor survival, high clinical stages and cancer metastasis. Role of MMPs in LC are multi-faced. MMPs are involved in drug resistance, induced CSCLs, participated in tumor immunity. Besides, MMPs polymorphisms may increase risk of LC. MMPs might be promising targets to restore the anti-tumor immune response and enhance the killing function of nature immune cells in LC.

Association of MMP7 T > C Gene Variant (rs10502001) and Expression in Chronic Obstructive Pulmonary Disease.

Patients with chronic obstructive pulmonary disease (COPD) have obstructed airflow through their lungs. Single nucleotide polymorphisms in matrix metalloproteinases (MMPs) genes and the risk of COPD have been the subject of numerous studies, with conflicting results. This investigation was conducted to determine whether the MMP7 (T>C) gene variant (rs10502001) was associated with an increased risk of COPD. A case-control study was conducted with 360 subjects (180 healthy controls and 180 COPD cases). The polymerase chain reaction (PCR)-restriction fragment length polymorphism method was used to genotype the SNP rs1050200. mRNA expression of MMP7 was performed using RT-PCR. The genotypic/allelic frequencies and carriage rates of rs10502001 (T>C) polymorphism were evaluated in 180 each of healthy controls and COPD cases. Cases have higher TC/CC genotype frequencies than controls. The "CC" genotype was found to be significantly associated with increased COPD risk (p = 0.016). The "C" allele frequency was higher in cases than in controls and showed significant association with COPD (p = 0.005). The carriage rate frequencies of T(-) and C(+) were significantly higher in cases than in controls (p = 0.031 and 0.047, respectively). MMP7 expression was significantly upregulated (p = 0.001) in COPD cases as compared with the controls. In addition, comparisons of MMP7 expression between the COPD cases with different genotypes showed that the "CC" genotype cases had significantly higher expression than those with "TT" genotype. The present findings showed statistically significant correlation of MMP7 (T>C) polymorphism and expression with COPD. Therefore, MMP7 responsible for degradation of elastin has been strongly linked to the progression of COPD.

Evaluation of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in human cases with orofacial clefts: A systematic review

The interaction between several cell populations or many genes and the coordination of multiple signal transmission pathways can lead to defects such as orofacial clefts (OFCs). Herein, a systematic review was designed to evaluate a group of important biomarkers (matrix metalloproteinases [MMPs] and tissue inhibitors of metalloproteinases [TIMPs]) in human cases with OFCs. Four databases including PubMed, Scopus, Web of Science, and Cochrane Library databases were searched until March 10, 2023, without any restriction. STRING, the protein-protein interaction (PPI) network software, was applied to investigate the functional interactions among the examined genes. The effect sizes including odds ratio (OR) dealing with a 95% confidence interval (CI), were extracted by the Comprehensive Meta-Analysis version 2.0 (CMA 2.0) software. Thirty-one articles were entered into the systematic review that four articles were analyzed in the meta-analysis. Single studies reported that several polymorphisms of MMPs (rs243865, rs9923304, rs17576, rs6094237, rs7119194, and rs7188573); and TIMPs (rs8179096, rs7502916, rs4789936, rs6501266, rs7211674, rs7212662, and rs242082) had an association with OFC risk. There was no significant difference for MMP-3 rs3025058 polymorphism in allelic (OR: 0.832; P=0.490), dominant (OR: 1.177; P=0.873), and recessive (OR: 0.363; P=0.433) models and MMP-9 rs17576 polymorphism in an allelic model (OR: 0.885; P=0.107) between the OFC cases and the controls. Based on immunohistochemistry reports, three MMPs (MMP-2, MMP-8, and MMP-9) and TIMP-2 had significant correlations with several other biomarkers in OFC cases. MMPs and TIMPs can impact the tissue and cells affected by OFCs and the process of apoptosis. The interaction between some biomarkers with MMPs and TIMPs (e.g., TGFb1) in OFCs can be interesting for future research.

Study on the Relationship between MMP-2, MMP-9 Gene Polymorphisms, and the Risk of Colorectal Cancer.

Objective The aim of the study is to explore the relationship between matrix metalloproteinase 2 (MMP-2) and matrix metalloproteinase 9 (MMP-9) gene polymorphisms and the risk of colorectal cancer. Methods From January 2019 to December 2021, 308 patients with colorectal cancer in our hospital were selected to be included in the colorectal cancer group and 300 normal healthy people were included in the control group. We perform genotyping, compare the genotype frequencies between the colorectal cancer group and the control group, calculate the relationship between MMP-2 and MMP-9 gene polymorphisms and disease risk, and analyze the genotype distribution characteristics of colorectal cancer patients with different pathological stages and lymph node metastasis status. The expression levels of serum MMP-2 and MMP-9 in patients with different genotypes were compared. Results The frequency of CC genotype and C gene at the MMP-2 gene−735 (C/T) locus in the colorectal cancer group was higher than that of the control group, and the frequency of TT genotype and T gene at MMP-9 gene−1562 (C/T) locus was a higher control group (P < 0.05). The comparison of genotype and gene frequency distribution of MMP-2 gene−1306 (C/T), −790 (T/G), and MMP-9 gene R668Q and P574R between the colorectal cancer group and the control group (P > 0.05); MMP-2 gene−735 (C/T) locus CC genotype and MMP-9 gene−1562 (C/T) locus TT genotype are dangerous genotypes for colorectal cancer. OR values were 1.490 (95% CI: 1.085–2.047), 1.519 (95% CI: 1.061–2.174); TNM stage III-IV, the proportion of CC genotype and TT genotype at MMP-9 gene−1562 (C/T) locus in patients with lymph node metastasis is higher than that without lymph node metastasis of TNM stage I-II patients (P < 0.05); MMP-2 gene in colorectal cancer patients. Serum MMP-2 levels in patients with CC genotype at 735 (C/T) locus were higher than those with CT + TT genotype, and serum MMP-9 levels in patients with TT genotype at MMP-9 gene−1562 (C/T) locus were higher CT + CC genotype patients (P < 0.05). Conclusion The CC genotype at −735 (C/T) locus of the MMP-2 gene and the TT genotype at−1562 (C/T) locus of the MMP-9 gene are risk genotypes for the development of colorectal cancer.

Is Matrix Metalloproteinase-9 Associated with Post-Stroke Cognitive Impairment or Dementia?

Matrix metalloproteinase-9 (MMP-9) is a significant protease required for synaptic plasticity, learning, and memory. Yet, the role of MMP-9 in the occurrence and development of cognitive decline after ischemic stroke is not fully understood. In this study, we used clinical data experiments to further investigate whether MMP-9 and genetic polymorphism are associated with post-stroke cognitive impairment or dementia (PSCID). A total of 148 patients with PSCID confirmed by the Montreal Cognitive Assessment (MoCA) 3 months after onset (PSCID group) were included in the study. The MMP-9 rs3918242 polymorphisms were analyzed using polymerase chain reaction coupled with restriction fragment length polymorphism, and the serum level of MMP-9 was measured using enzyme-linked immunosorbent assay (ELISA). The same manipulations have been done on 169 ischemic stroke patients without cognitive impairment (NCI group) and 150 normal controls (NC group). The expression level of serum MMP-9 in the PSCID group and NCI group was higher compared to the NC group, and the levels in the PSCID group were higher than that in the NCI group (all p < 0.05). Diabetes mellitus, hyperhomocysteinemia, and increased serum MMP-9 levels were the main risk factors of cognitive impairment after ischemic stroke. The serum level of MMP-9 was negatively correlated with the MoCA score, including visual-spatial executive, naming, attention, language, and delayed recall. Genetic polymorphism showed that TC genotype with MMP-9 rs3918242 and CC genotype were associated with a significantly increased risk of PSCID; moreover, the TC genotype significantly increased the risk of cognitive impairment. In the TCCC genotype of MMP-9 rs3918242, diabetes mellitus and hyperhomocysteinemia were associated with the increased risk of PSCID; also, hyperhomocysteinemia could increase the risk of cognitive impairment. MMP-9 level and MMP-9 rs3918242 polymorphism have an important role in the occurrence and development of post-stroke cognitive impairment or dementia (PSCID).

Proteases and HPV-Induced Carcinogenesis

Simple SummaryHuman papillomavirus (HPV) infection is a sexually transmitted disease with high prevalence worldwide. Although most HPV infections do not lead to cancer, some HPV types are correlated with the majority of cervical cancers, and with some anogenital and oropharyngeal cancers. Moreover, enzymes known as proteases play an essential role in the pathogenic process in HPV-induced carcinogenesis. This review highlights the role of proteases and recent epidemiological data regarding HPV-dependent carcinogenesis.Persistent infection with Human papillomavirus (HPV) is the main etiologic factor for pre-malignant and malignant cervical lesions. Moreover, HPV is also associated with oropharynx and other anogenital carcinomas. Cancer-causing HPV viruses classified as group 1 carcinogens include 12 HPV types, with HPV 16 and 18 being the most prevalent. High-risk HPVs express two oncoproteins, E6 and E7, the products of which are responsible for the inhibition of p53 and pRB proteins, respectively, in human keratinocytes and cellular immortalization. p53 and pRB are pleiotropic proteins that regulate the activity of several signaling pathways and gene expression. Among the important factors that are augmented in HPV-mediated carcinogenesis, proteases not only control processes involved in cellular carcinogenesis but also control the microenvironment. For instance, genetic polymorphisms of matrix metalloproteinase 1 (MMP-1) are associated with carcinoma invasiveness. Similarly, the serine protease inhibitors hepatocyte growth factor activator inhibitor-1 (HAI-1) and -2 (HAI-2) have been identified as prognostic markers for HPV-dependent cervical carcinomas. This review highlights the most crucial mechanisms involved in HPV-dependent carcinogenesis, and includes a section on the proteolytic cascades that are important for the progression of this disease and their impact on patient health, treatment, and survival.

Role of Single Nucleotide Polymorphism of Matrix Metalloproteinase (MMP-13 rs2252070) in the Etiology of Dental Caries: A PCR Based Study

Role of Single Nucleotide Polymorphism of Matrix Metalloproteinase (MMP-13 rs2252070) in the Etiology of Dental Caries: A PCR Based Study

Association between matrix metalloproteinase-3 gene polymorphisms and tendon-ligament injuries: evidence from a meta-analysis

BackgroundTendon-ligament injuries (TLIs), including Achilles tendinopathy, cruciate ligament injury, tennis elbow, rotator cuff injury, patellar tendinopathy, and tibial tendinopathy, are common musculoskeletal soft injuries during physical activity. Matrix metalloproteinase-3 (MMP-3) gene polymorphisms have been implicated in the etiology of TLIs in several genetic association studies with inconsistent results. The purpose of this study was to collect and synthesize the current evidences on the association of MMP-3 polymorphisms and TLIs.MethodsThe search was conducted using PubMed, Web of Science, EMBASE, Cochrane Library, CNKI and Wanfang databases, prior to July, 2021. Newcastle Ottawa Scale was used to appraise the study quality. Strengths of association were represented by odds ratios (ORs) and 95% confidence intervals (95% CIs).ResultsThirteen studies with 2871 cases and 4497 controls met the eligibility criteria, and each study was in high quality. The overall analyzes suggested rs3025058 was associated with an increased TLIs risk (5A vs. 6A, OR = 1.20, 95% CI 1.03–1.40, P = 0.020). However, the association was not found for rs679620, rs591058, and rs650108 polymorphisms. Subgroup analysis by injury type suggested that rs679620 polymorphism was associated with a reduced risk to Achilles tendon rupture (AA + AG vs. GG, OR = 0.46, 95% CI 0.25–0.87, P = 0.020), and rs3025058 was associated with an elevated risk to anterior cruciate ligament injury (5A5A + 5A6A vs. 6A6A, OR = 1.46, 95% CI 1.03–2.06, P = 0.030). When stratified by ethnicity, the findings indicated that rs3025058 polymorphism was associated with an increased TLIs risk among Caucasians (5A6A vs. 6A6A, OR = 1.55, 95% CI 1.09–2.42, P = 0.020) and Brazilians (5A5A vs. 5A6A + 6A6A, OR = 2.80, 95% CI 1.44–5.45, P = 0.002).ConclusionFindings of this study suggest that rs679620 polymorphism is associated with a reduced Achilles tendon rupture risk, and rs3025058 polymorphism contributes to an increased TLIs risk in Caucasians and Brazilians. However, rs591058 and rs650108 polymorphisms do not show any association with TLIs.

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.

Correlations of MMP-9 and PPARγ gene polymorphisms with occurrence of preeclampsia.

The aim of this study was to investigate the expressions of matrix metalloproteinase-9 (MMP-9) and peroxisome proliferator-activated receptor gamma (PPARγ) in the placenta of patients with preeclampsia and to elucidate the associations of their polymorphisms with the occurrence of preeclampsia. A total of 200 patients with preeclampsia (Preeclampsia group) and 100 pregnant women with normal delivery (Control group) were enrolled as research subjects. The expressions of MMP-9 and PPARγ in placentae of Preeclampsia group and Control group were measured by Western blotting. Conformation-difference gel electrophoresis was adopted for typing single nucleotide polymorphisms (SNPs) rs101201 and rs23102 in the promoter region of MMP-9 gene and rs201018 and rs102934 in the promoter region of PPARγ gene. Chi-square test was conducted to analyze whether the distribution frequency of MMP-9 and PPARγ genotypes was consistent with the law of genetic equilibrium. The correlations of the alleles and polymorphisms of MMP-9 and PPARγ with the occurrence of preeclampsia were analyzed. In addition, the associations of rs101201 genotype GG of MMP-9 gene and rs201018 genotype TT of PPARγ gene with the clinicopathological features of preeclampsia were analyzed. Compared with Control group, the protein expression level of MMP-9 was significantly down-regulated (p<0.05), while the protein expression level of PPARγ was significantly up-regulated in placental tissues of Preeclampsia group (p<0.05). Based on Hardy-Weinberg equilibrium analysis, the two polymorphisms of both MMP-9 and PPARγ were consistent with the genetic equilibrium distribution (p>0.05). Gene correlation analysis showed that rs101201 polymorphism and its alleles in the promoter region of MMP-9 gene and rs201018 polymorphism and its alleles in the promoter region of PPARγ gene were correlated with the occurrence of preeclampsia (p<0.05). Besides, body mass index (BMI) value, gestational age, systolic blood pressure, and serum creatinine level in preeclampsia patients with the genotype GG of rs101201 in the promoter region of MMP-9 gene were not statistically significantly different from those in Control group (p>0.05). Furthermore, no statistically significant differences were observed in gravidity, parity, gestational age, systolic blood pressure, serum creatinine level, and plasma albumin level between preeclampsia patients with the genotype TT of rs201018 in the promoter region of PPARγ gene and those in Control group (p>0.05). PPARγ and MMP-9 are abnormally expressed in the placenta of patients with preeclampsia. Moreover, rs201018 polymorphism in the promoter region of PPARγ gene and rs101201 polymorphism in the promoter region of MMP-9 gene are correlated with the occurrence of preeclampsia.

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.

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.

The role of gene-gene and gene-environmental interactions of polymorphic matrix metalloproteinases loci in the formation of the risk of stroke in men with hypertension

Analysis of the role of genetic polymorphisms of matrix metalloproteinases (MMPs), their gene-gene and gene-environment interactions in the formation of ischemic stroke in men with arterial hypertension (AI). The study included 523 men with arterial hypertension: 201 patients with ischemic stroke and 322 patients without stroke. The association of MMPs loci with stroke with hypertension was determined by logistic regression analysis in dominant, recessive, additive genetic models in PLINK v.2.050. For five SNPs co-located on chromosome 11 (314.3 kb), haplotypic analysis was performed, the relationship of haplotypes with stroke development was determined by the EM algorithm. Gene-gene and gene-environment interactions of MMPs with smoking and alcohol consumption during stroke development were evaluated by GMDR (Generalized Multifactor Dimensionality Reduction) using GMDR v.0.9 software. Polymorphic locus rs3025058 is associated with stroke in men in dominant and additive genetic models (OR=0.63-0.74, pperm=0.03). Four haplotypes of MMPs have a protective effect on the development of stroke with hypertension (OR=0.48-0.50, pperm=0.02-0.03). Four models of gene-gene interactions of polymorphic MMPs loci (OR=2.19-2.55, pperm<0.001) and three four-factor models of gene-environment interactions of MMPs with alcohol abuse (OR=2.82-3.11, pperm<0.001) are associated with a high risk of ischemic stroke in men with hypertension. rs3025058, rs1320632, rs11225395 and rs1799750 demonstrate the greatest contribution to gene-gene and gene-environment interactions in the formation of AI. Thus, the results of the study indicate that the interactions of MMPs genes with each other and with modifiable environmental factors play a significant role in the development of stroke with hypertension in men.

ASSOCIATION OF MMP-9 GENETIC POLYMORPHISM AND ММР-9 CONCENTRATION WITH ECHOCARDIOGRAPHIC PARAMETERS IN UKRAINIAN PATIENTS WITH CORONARY ARTERY DISEASE

Introduction. Cardiovascular diseases are the main cause of reduced life expectancy, workability, and death among the people of Eastern Europe. Matrix metalloproteinase-9 (MMP-9) is known as one of the leading factors involved in the development and progression of atherosclerosis and heart remodeling. The increasing sizes of the heart’s chambers lead to changes in the electrophysiological properties of the myocardium and to the subsequent occurrence of arrhythmias and conduction disorders. Materials and methods. The study included 25 patients with intact coronary arteries (CA), 40 patients with acute coronary syndrome (ACS) and 63 patients with chronic coronary syndrome (CCS) to investigate the effect of MMP-9 polymorphism and its serum concentration on changes in echocardiographic parameters. Real-time PCR was carried out for genotyping on the rs17567-polymorphic locus and ELISA study was performed to measure the MMP-9 plasma concentration. Results. Statistically significant differences were found in the thickness of the posterior wall of the heart among carriers of the G-allele and AA-homozygotes for the MMP-9 rs17576-single nucleotide polymorphism but only in patients with ACS. The size of the left ventricle posterior wall can be predicted for carriers of these genotypes. Conclusions. The study revealed no statistically significant relationship between MMP-9 concentration and echocardiographic parameters in patients with ACS and CCS. However, there were statistically significant differences in the left atrium diameter and thickness of the posterior wall of the left ventricle depending on the genotype for MMP-9 rs17576-single nucleotide polymorphism only in patients with ACS. The size of the posterior wall of the left ventricle can be predicted for carriers of AG and GG genotypes.

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.

Correlation between matrix metalloproteinase-2 polymorphisms and first and recurrent atherosclerotic ischemic stroke events: a case-control study.

ObjectiveTo determine the associations between matrix metalloproteinase-2 (MMP-2, encoded by the MMP2 gene) 1306C/T and 735C/T polymorphisms and first and recurrent ischemic stroke in a Chinese population.MethodsPatients with first and recurrent ischemic stroke were included. Serum MMP-2 was measured, and MMP2 1306C/T and 735C/T polymorphisms were detected. The associations between MMP2 1306C/T and 735C/T polymorphisms and first and recurrent ischemic stroke were analyzed.ResultsSerum MMP-2 in patients with first and recurrent ischemic stroke was significantly higher compared with controls, and patients with recurrent ischemic stroke had higher MMP-2 than those with first ischemic stroke. The frequency of the CC genotype and C allele of MMP2 735C/T was highest in patients with recurrent ischemic stroke, followed by patients with first ischemic stroke, and controls. Conversely, the genotype and allele of MMP2 1306C/T did not significantly differ between groups. The CC genotype of MMP2 735C/T was independently associated with first and recurrent ischemic stroke (odds ratios = 1.45 and 1.64, respectively), as was the C allele of MMP2 735C/T (odds ratios = 1.68 and 1.77, respectively).ConclusionsThe CC genotype and C allele of MMP2 735C/T were associated with first and recurrent ischemic stroke in a Chinese population.