MMP-9 Polymorphisms Research Articles

Gender Difference in the Link of MMP-9 Gene Polymorphism to Serum Matrix Metalloproteinase Level in the Determination of Lung Function in South Indian Population

Background and Aim: Matrixins or matrix metalloproteinases (MMP) belong to metzincin superfamily and they are involved in many physiological functions like extracellular matrix remodeling, angiogenesis, bone growth and neuritic growth. Polymorphisms in MMP-9 gene will result in over expression of matrix metalloproteinases leading to excessive extracellular matrix degradation, which cannot be overcome by the anti-proteinases. One such polymorphism of MMP-9 is Gln279Arg. Degradation of pulmonary matrix can lead to chronic obstructive pulmonary disease. Studies in the past have demonstrated female preponderance in incidence of COPD among smokers. Methods: This was a cross sectional study conducted among healthy volunteers of age group 18 to 45 years. Pulmonary function tests of the subjects were recorded using computerised spirometry (SPIROLAB III). Frequency of Gln279Arg polymorphism was estimated by RT-PCR. Serum MMP-9 were estimated by Enzyme linked Immunosorbent Assay. Results: MMP-9 levels were found to be elevated in AA genotype group in females. Conclusion: The females with AA genotype, have increased MMP-9 levels and so they may be more prone for COPD if they are exposed to the environmental risk factors.

MMP-2 and MMP-9 gene polymorphisms and risk of head and neck carcinomas

Abstract Background: Head and neck carcinomas (HNC) account for a majority of ear, nose and throat tumours. They account for 6.3% of all incident malignancies and 6.2 % of all deaths from cancer in Romania in 2020, the fifth most common cancer in this Eastern Europe country. Aim of the study: The aim of our study was to investigate the association between two MMP-2 and MMP-9 promoter gene polymorphisms and head and neck cancer. Methods. We enrolled 142 subjects, 65 cancer patients, and 77 control subjects and tested them for MMP-2 -735 C/T and MMP-9 -1562 C/T polymorphisms by PCR-RFLP. Results. Comparison between cancer patients and controls demonstrated the presence of MMP-2 -735 C/T and MMP-9 -1562 C/T in head and neck malignant tumours, with OR = 2.206 (95% CI 1.058-4.599, P = 0.03) for MMP-2 and OR = 2.748 (95% C.I. 1.262-5.981, P=0.009) for MMP-9 gene polymorphism. This means that the presence of T allele could be a risk factor for head and neck cancer development. The analysis included a stratification of studied groups by age and gender. Conclusions. Both genotypes were associated with a significant risk for head and neck carcinomas in case of the presence of the T allele. MMP-2 -735 C/T (rs2285053) and MMP-9 -1562 C/T (rs3918242) gene polymorphism could be an important genetic marker for head and neck cancer susceptibility. This finding could be useful for genetic screening in head and neck carcinomas.

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

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

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

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

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

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

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

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

Coronary artery disease association with serum concentration and genetic variation of MMP-9 in Ukrainian population

Abstract Introduction Coronary artery disease (CAD) is one of the main cause of death in European countries. The mortality associated with CAD has been rising for the past 30 years in Central and Easten Europe (including Ukraine). It is known that atherosclerosis is the primary risk factor of CAD development and Matrix metalloproteinase-9 (MMP-9) is involved in all stages of atherosclerosis and thus may contribute to CAD aggravation. It is very important to find specific mechanisms of atherosclerosis progression, the impact of genetic and external factors which influence on the development of CAD in different populations. Therefore, the aim of this study was to investigate the influence of MMP-9 concentration and functional rs17576 single nucleotide polymorphism (SNP) on risk of CAD development in Ukrainian population. Materials and methods In our study 128 patients were recruited. All of them we divided into three groups: 1 - with angiogrphically normal (intact) coronary arteries; 2 - patients with acute coronary syndrome (ACS) and 3 - with chronic coronary syndrome (CCS). The study protocol was approved by the Institutioal Ethics Committee and each participant was required to provide a writing informed consent. We recorded clinical data, biochemical analysis, performed electrocardiogram, coronary angiography and echocardiography. Blood for detection of MMP-9 and rs 17567 MMp-9 polymorphism was draw under standardized conditions before coronary angiography. Levels of MMP-9 were assessed using commercial ELISA immunoassay following manufacturer's instruction. The genotyping for MMP-9 rs17567-single nucleotide polymorphism was done by Real-time PCR. All statistical calculations were done using Statistical Package for the Social Sciences software. Results The results of analysis of association between MMP-9 rs17576 and CAD development demonstrate a weak link with borderline significance between MMP-9 concentration and ACS presence both before (Pc=0.026; ORc=1.003, 95% CI: 1–1.006) and after the adjustment for covariates (Pa=0.04; ORa=1.003, 95% CI: 1–1.006). In contrast, no significant association was detected for CCS group (Pa&amp;gt;0.05). There were no statistically significant differences in genotype and allele frequencies in compared groups (P&amp;gt;0.05) and association between MMP-9 serum concentration and MI occurrence. But we found the statistically significant differences in genotypes distribution (P=0.025) while the alleles distribution was similar (P&amp;gt;0.05) among compared groups. Additionally, AG-carriers had the lower risk of MI development in crude (Pc=0.033; ORc=0.359, 95% CI: 0.14–0.922) and adjusted (Pa=0.023; ORa=0.299, 95% CI: 0.106–0.848) overdominant model of inheritance. Conclusion In the present research we have analyzed the link of MMP-9 serum concentration and MMP-9 rs17567-polymorphic variant with CAD development among Ukrainians. We found lower risk of MI occurrence for AG-carriers. Funding Acknowledgement Type of funding sources: None.

Genetic associated complications of type 2 diabetes mellitus.

According to the International Diabetes Federation, the number of adults (age of 20-79) being diagnosed with diabetes mellitus (DM) have increased from 285 million in year 2009 to 463 million in year 2019 which comprises of 95% type 2 DM patient (T2DM). Research have claimed that genetic predisposition could be one of the factors causing T2DM complications. In addition, T2DM complications cause an incremental risk to mortality. Therefore, this article aims to discuss some complications of T2DM in and their genetic association. The complications that are discussed in this article are diabetic nephropathy, diabetes induced cardiovascular disease, diabetic neuropathy, diabetic foot ulcer (DFU) and Alzheimer's disease (AD). According to the information obtained, genes associated with diabetic nephropathy (DN) are gene GABRR1 and ELMO1 that cause injury to glomerular. Replication of genes FRMD3, CARS and MYO16/IRS2 shown to have link with DN. The increase of gene THBS2, NGAL, PIP, TRAF6 polymorphism, ICAM-1 encoded for rs5498 polymorphism and C667T increase susceptibility towards DN in T2DM patient. Genes associated with cardiovascular diseases are adiponectin gene (ACRP30) and apolipoprotein E (APOE) polymorphism gene with ξ2 allele. Haptoglobin (Hp) 1-1 genotype and mitochondria superoxide dismutase 2 (SOD2) plays a role in cardiovascular events. As for genes related to diabetic neuropathy, janus kinase (JAK), mutation of SCN9A and TRPA1 gene and destruction of miRNA contribute to pathogenesis of diabetic neuropathy among T2DM patients. Expression of cytokine IL-6, IL-10, miR-146a are found to cause diabetic neuropathy. Besides, A1a16Va1 gene polymorphism, an oxidative stress influence was found as one of the gene factors. Diabetic retinopathy (DR) is believed to have association with monocyte chemoattractant protein-1 (MCP-1) and insulin-like growth factor 1 (IGF1). Over-expression of gene ENPP1, IL-6 pro-inflammatory cytokine, ARHGAP22's protein rs3844492 polymorphism and TLR4 heterozygous genotype are contributing to significant pathophysiological process causing DR, while research found increases level of UCP1 gene protects retina cells from oxidative stress. DFU is manifested by slowing in re-epithelialization of keratinocyte, persistence wound inflammation and healing impairment. Re-epithelialization disturbance was caused by E2F3 gene, reduction of Tacl gene encoded substance P causing persistence inflammation while expression of MMp-9 polymorphism contributes to healing impairment. A decrease in HIF-1a gene expression leads to increased risk of pathogenesis, while downregulation of TLR2 increases severity of wound in DFU patients. SNPs alleles has been shown to have significant association between the genetic dispositions of T<inf>2</inf>DM and AD. The progression of AD can be due to the change in DNA methylation of CLOCK gene, followed with worsening of AD by APOE4 gene due to dyslipidemia condition in T2DM patients. Insulin resistance is also a factor that contributes to pathogenesis of AD.

MMP-1 (519 A/G) and TIMP-1 (372 T/C) genes polymorphism in an Egyptian sample of Acne vulgaris patients.

Different Matrix metalloproteinases (MMPs) family members may be implicated in acne vulgaris development. However, there are no published data about the role of MMP-1 and TIMP-1gene polymorphisms in acne vulgaris development. To evaluate the association between MMP-1 (519 A/G) and TIMP-1 (372T/C) gene polymorphisms and the risk of developing acne vulgaris among a sample of Egyptian acne patients. This case-control study included 100 acne vulgaris patients and 120 apparently healthy control subjects. Acne severity was assessed according to Global Acne Grading System (GAGS). MMP-1 (519 A/G) and TIMP-1 (372T/C) gene polymorphisms were investigated using RFLP-PCR technique. The MMP-1 (519 A/G) AG and GG genotypes and G allele increase the risk of acne vulgaris~2-3 folds. In female patients, TIMP-1 (372 C/T) TT genotype and T allele showed significantly higher frequency in cases compared with the control group (p=0.004, 0.001 respectively) with a higher risk to develop acne. On the other hand, in male patients, there was insignificant difference between the frequency of alleles in patients and control subjects. TIMP-1 (372C/T) TT genotype has been shown to be significantly detected in the studied female patients associated with the positive family history of the disease, and it increases the risk of back affection, severe acne grade development, and the liability to postacne scar formation. MMP-1 (519 A/G) and TIMP-1 (372T/C) gene polymorphisms may be related to acne vulgaris development.

MMP-2 and MMP-9 Polymorphisms and Preeclampsia Risk in Tunisian Arabs: A Case-Control Study

The abnormal production of matrix metalloproteinases (MMPs), especially MMP-9 and MMP-2, plays a pivotal role in hypertensive disorders of pregnancy, and as such, can influence the development of preeclampsia. These alterations may result from functional genetic polymorphisms in the promoter region of MMP-9 and MMP-2 genes, which modify MMP-9 and MMP-2 expression. We investigated the association of MMP-9 polymorphism rs3918242 (-1562 C>T) and MMP-2 polymorphism rs2285053 (-735 C>T) with the risk of preeclampsia. This case–control study was conducted on 345 women with preeclampsia and 281 age-matched women with normal pregnancies from Tunisian hospitals. Genomic DNA was extracted from whole blood collected at delivery. Genotypes for -1562 C>T and -735 C>T polymorphisms were performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). An increased frequency of heterozygous MMP-9 -1562 C/T genotype carriers was observed in women with preeclampsia compared to healthy controls (p = 0.03). In contrast, the MMP-2 -735 C>T polymorphism was not significantly different regarding frequency distribution of the allele and genotype between healthy pregnant women and women with preeclampsia. Our study suggests that the MMP-9 -1562 C/T variant, associated with high MMP-9 production, could be a genetic risk factor for preeclampsia in Tunisian women.

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

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

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

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

ASSOCIATION OF ARTERIAL STIFFNESS WITH AGT, ACE, NOS3, TNF, MMP9, CYBA POLYMORPHISM IN HEALTHY ADULTS

Abstract Objective: Arterial stiffness (AS) is a prominent risk factor for cardiovascular diseases. It is known that different polymorphisms are associated with cardiovascular diseases, while there is insufficient evidence that genetic traits lead to arterial wall changes, including AS. The aim of this study was to find the association between increased AS and polymorphisms that are associated with cardiovascular diseases and are involved in renin-angiotensin-aldosterone system, chronic inflammation and oxidative stress in healthy adults. Design and method: We investigated 153 healthy adults, mean age 50.56 ± 13.14 years, 35% male, 22% smokers. Increased AS was defined as pulse wave velocity (PWV) &gt; 10 m/s. Measurements were performed by applanation tonometry using SphygmoCor device (AtCor, Australia). Insulin resistance was diagnosed if HOMA IR was &gt; 2,5. Leucocyte telomere length (LTL) were measured by real-time PCR. AGT, ACE, NOS3, TNF, MMP9 polymorphisms were detected by real-time PCR using DNA technologies (Russia) standard kits, and CYBA polymorphism was detected by Applied Biosystems (USA) standard kit. Associations of genotypes and alleles with increased PWV were studied using chi-square or Fisher's exact test. Multiple logistic regression models were created to identify the effect of genotype and risk factors on PWV. Results: Increased AS was associated with D-allele (OR = 1.89, 95% CI: 1.16–3.12, p = 0.014) and DD-genotype (OR = 3.42, 95% CI: 1.39–9.36, p = 0.005) of ACE Ins &gt; Del polymorphism. ACE Ins &gt; Del polymorphism predicted increased AS along with sex, age and LTL. The results of multiple logistic regression analysis are represented in the table. Conclusions: In healthy adults increased AS is strongly associated with DD-genotype of ACE polymorphism, sex, age and leucocyte telomere length

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

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

Investigation of association between genetic polymorphisms of MMP2, MMP8, MMP9 and TIMP2 and development of varicose veins in the Slovak Population - pilot study.

Matrix metalloproteinases (MMPs) are a family of zinc-dependent metalloendopeptidases that degrades extracellular matrix (ECM) components. MMPs are associated with venous wall remodelling, proliferation, migration, phenotypic and functional transformation of vascular smooth muscle cells and ECM organization under the physiological and pathophysiological conditions. We investigated possible association of genetic promoter polymorphisms of MMP2 (rs243866), MMP8 (rs11225395), MMP9 (rs3918242) and TIMP2 (rs8179090) to varicose veins development in the Slovak population. Genomic DNA from 276 Slovak individuals (138 cases, 138 controls) was genotyped for selected SNPs (rs243866, rs11225395, rs3918242 and rs8179090) using the PCR-RFLP analysis. The data were analysed by chi-squared (chi2) test, logistic regression, and Mann-Whitney test. The risk of varicose veins development was evaluated in dominant, codominant and recessive genetic models. The statistical evaluation of selected polymorphisms in patients in all three genetic models has not shown a significant risk of varicose veins development. Our study has not shown the association between selected polymorphisms and increased risk of varicose veins development in Slovak population. More evidence with broaden sample size is needed.

Polymorphisms of matrix metalloproteinase-7 and -9 are associated with oral tongue squamous cell carcinoma.

Matrix degradation is an important event in the progression, invasion and metastasis of malignant head and neck lesions. Imbalances, mutations and polymorphisms of MMPs and their inhibitors are observed in several cancer subtypes. The aim of this study was to evaluate the association of the MMP-7 gene promoter (181 A/G) and MMP-9 (-1562 C/T) polymorphisms in oral tongue squamous cell carcinoma (OTSCC). MMP-7 (rs11568818) and MMP-9 (rs3918242) single-nucleotide polymorphisms (SNPs) were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis in 71 cases of OTSCC. Normal tissue specimens were obtained from 60 healthy volunteers to serve as the control. The MMP-7 G allele and MMP-9 T allele were more frequent in the OTSCC group than the control group, but only when these two SNPs were taken together was a significant association found with the nodal metastasis of OTSCC (p < 0.001). Based on our results, SNPs in the promoter region of MMP-7 and MMP-9 appear to be associated with greater risk of developing OTSCC, and with a higher propensity to form metastatic tumors. In this respect, molecular studies investigating polymorphisms may be useful in predicting tumor behavior.

Hypertrophic post-acne scarring is associated with a single nucleotide polymorphism (rs243865) in the matrix metalloproteinase-2 gene.

Aberrant tissue expression of matrix metalloproteinases has been observed in acne. Our objective was to study the relevance of MMP-2 (-1306 C/T, rs243865) and TIMP-2 (-418 G/C, rs8179090) single nucleotide polymorphisms (SNP) in acne and post-acne scarring. 512 patients (169 having acne without scarring, 319 having atrophic acne scarring, 24 having hypertrophic acne scarring) and 161 age-matched controls were recruited from the Dermatology Outpatient Department after obtaining informed written consent. Venous blood (5 ml) was collected for genotyping by Polymerase Chain Reaction (PCR)-Restriction Fragment Length Polymorphism (RFLP) method. The severity of acne and acne-scarring were graded. Males had a significantly increased risk of developing severe acne (P = 0.012), extra-facial acne (P = 0.047) and extra-facial acne scarring (P = 0.0001). The presence of inflammatory acne positively correlated with severity of scarring (P = 0.001). Subjects with a homozygous CC genotype of MMP-2 (-1306 C/T) had 1.0, 7.8 and 8.2 times the odds of developing hypertrophic scarring when compared to controls (P = 0.05, 95% CI: 0.7-1.6), subjects having acne without scarring (P = 0.047, 95% CI: 1.0-59.9) and subjects having atrophic scarring, respectively (P = 0.041, 95% CI: 1.1-59.9). A significant association was observed between hypertrophic post-acne scarring and the CC genotype of MMP-2 (-1306 C/T).

Matrix metalloproteinase (MMP)-1 and MMP-3 gene variations affect MMP-1 and -3 serum concentration and associates with breast cancer.

Matrix metallopeptidases (MMPs) 1 and 3 have been shown to contribute to the initiation, and progression of different cancers, including breast cancer (BC). In this study, we aimed to examine the relations between polymorphisms of MMP1 (rs1799750) and MMP3 (rs632478) and their circulating levels with BC. The polymorphisms were genotyped by PCR-based Restriction Fragment Length Polymorphism (RFLP) and Allele-Specific PCR (AS-PCR) among 100 patients and 100 controls. MMP1 and MMP3 serum levels were measured by enzyme-linked immunosorbent assay (ELISA). Genotype distributions of MMP1 and MMP3 genes showed significant difference between patients and controls. The distribution of 2G/2G, 1G/2G and 1G/1G genotypes for MMP1 was 74%, 2% and 24% in the patients and 38%, 2% and 60% in the controls, respectively (P = 0.0001). For MMP3 the distribution of C/C, A/C and A/A genotypes was 28%, 54% and 18% in patients and 48%, 40% and 12% in controls, respectively (P = 0.01). For MMP1, the 2G/2G genotype was linked with a higher risk of BC when compared with that of the 1G/1G genotype (OR = 4.86; 95% CI = 2.63-8.99; P = 0.0001). For MMP3, in co-dominant model, there was a higher risk of BC in A/A and A/C genotype carriers (A/A: OR = 2.57; 95% CI = 1.08-6.11; P = 0.03) (A/C: OR = 2.31 95% CI = 1.24-4.30; P = 0.008). We also showed that MMP1 and MMP3 serum level was significantly increased in BC patients compared to controls. MMP1 and MMP3 genetic variations and their circulating levels are both significantly related to BC.

Activities and polymorphisms of MMP-2 and MMP-9, smoking, diabetes and risk of prostate cancer.

Matrix metalloproteinases (MMPs) are a group of zinc dependent enzymes that are involved in tumor cell invasion and metastasis. The role of MMP-2 and -9 genetic polymorphism in different malignancies has been the subject of numerous studies. The present research has attempted to discover any positive correlation between MMP-2 and MMP-9 SNPs and prostate cancer (PCa) in patients with a history of either diabetes or smoking habits. 112 PCa-patients and 150 unrelated healthy-controls that matched for age and sex were selected for present case-control study. MMP-2 -1575G/A and MMP-9 -1562 C/T polymorphisms detected by PCR-RFLP, serum tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2), testosterone, prostate-specific antigen (PSA), free-prostate-specific-antigen (fPSA), and fPSA/PSA levels were detected by ELISA and enzyme assay, respectively. MMP-2 and MMP-9 activities were measured by gelatin-zymography. Covariates were considered as age, status of cigarette smoking, and a possible history of diabetes mellitus (DM). The frequency of -1575 MMP-2 A/A + A/G and -1562 MMP-9 C/T + T/T genotypes were higher in PCa-patients with DM (74.3%,p = 0.003) and with smoking habits (72.5%,p = 0.005). These genotypes were associated with the increased risk of prostate cancer in smokers (3.52-folds) and in individuals with history of DM (4.34-folds). A significant positive association was found between level of TIMPs (TIMP -1 and TIMP-2) and BMI in PCa-patients and also between testosterone levels and MMP-9 activity in healthy control subjects. For the first time, this study demonstrated that activities of MMP-2 -1575G/A and MMP-9 -1562C/T variants in association with smoking and diabetes are considered significant risk factors for PCa.

PERAN POLIMORFISME GEN MATRIKS METALLOPROTEINASE-9 DENGAN KEJADIAN PENYAKIT PARU OBSTRUKTIF KRONIK

Excessive secretion of MMP-9 is one of the cause of COPD is which can cause undesirable lung tissue degradation. Increased expression of MMP-9 is associated with increased gene promoter activity. The purpose of this study was to determine the role of mettaloproteinase-9 matrix gene polymorphisms with COPD events. This was a case-control study. With a total sample of 60 patients consisting of 30 COPD patients and 30 non-COPD patients. Samples were amplified by PCR (Polymerase Chain Reaction) The results of DNA amplification were digested with SphI restriction enzyme to see the allele variant of MMP-9 C-1562T. Visualization of restriction results with 2% agarose gel electrophoresis will show 2 bands on the T allele (188bp, 247bp), 1 band on the C allele (435bp). The results obtained were homozygous CC variants in COPD 20 (66.67%) and non-COPD 21 (70%). Heterozygous variant of CT 10 (33.33%) in COPD and 9 (30%) in non-COPD. TT variant is not found at all. Based on the results obtained by the most CC homozygous variants in COPD (66.67%) and non-COPD (70%) and no association was found between MMP-9 polymorphism and COPD events (p&gt; 0.05). Based on the results of this study, there is no significant relationship that we can conclude.