Matrix Metalloproteinase-3 Genotype Research Articles

Impacts of Matrix Metalloproteinase-2 Promoter Genotypes on Breast Cancer Risk.

Matrix metalloproteinase-2 (MMP-2) has been implicated in the pathogenesis of breast cancer (BC). However, there is limited research on the role of MMP-2 genotypes in BC risk. This study aimed to investigate the associations between two MMP-2 promoter polymorphisms, rs243865 and rs2285053, and BC risk. MMP-2 genotypes were analyzed using PCR-based RFLP methodology in a cohort comprising 1,232 BC cases and 1,232 controls. Genotypic frequencies of MMP-2 rs243865 and rs2285053 in controls were consistent with Hardy-Weinberg equilibrium (p=0.3702 and 0.2036, respectively). There were no significant differences in the distribution of rs243865 and rs2285053 genotypes between BC cases and controls (p for trend=0.1602 and 0.2170, respectively). Variant genotypes at rs243865 and rs2285053 appeared to confer a protective effect, although not statistically significant (all p>0.05). Similarly, the variant T allele at rs243865 and rs2285053 showed a non-significant trend towards decreased BC risk (OR=0.84 and 0.89, 95%CI=0.69-1.02 and 0.78-1.02, p=0.0811 and 0.1043, respectively). There was no interaction observed between MMP-2 rs243865 or rs2285053 genotypes and age. Stratified analysis did not reveal significant associations between MMP-2 rs243865 or rs2285053 genotypes and triple-negative breast cancer (TNBC) (p=0.6458 and 0.8745, respectively). Among both TNBC and non-TNBC cases, none of the variant genotypes at rs243865 or rs2285053 showed significant associations with TNBC (all p>0.05). MMP-2 rs243865 and rs2285053 genotypes appear to have a minimal impact on individual susceptibility to BC or TNBC.

Association of Matrix Metalloproteinase-9 Genotypes With Lung Cancer Risk in Taiwan.

Matrix metalloproteinase-9 (MMP-9) expression is upregulated in various diseases, including lung cancer. However, the role of MMP-9 genotype in lung cancer susceptibility remains uncertain. This study aimed to clarify the contribution of MMP-9 promoter rs3918242 genotypes to the risk of lung cancer in Taiwan. The MMP-9 rs3918242 genotypes of 358 lung cancer patients and 716 healthy controls were determined using polymerase chain reaction-restriction fragment length polymorphism methodology. Individuals carrying the variant CT or TT genotype of MMP-9 rs3918242 did not demonstrate an increased risk of lung cancer compared to wild-type CC carriers [odds ratio (OR)=1.11 and 1.85, 95% confidence interval (95%CI)=0.82-1.48 and 0.91-3.76; p=0.5541 and 0.1280, respectively]. Moreover, individuals carrying the T allele did not show a higher lung cancer risk compared to those with the C allele (OR=1.21, 95%CI=0.95-1.54, p=0.1444). However, a significant association was observed between the MMP-9 rs3918242 TT genotype and lung cancer risk among non-smokers (OR=5.48, 95%CI=1.31-22.89, p=0.0181). The presence of the TT genotype for MMP-9 rs3918242 may indicate an elevated risk of lung cancer among non-smokers.

Impacts of Matrix Metalloproteinase-9 Promoter Genotypes on Asthma Risk.

The overexpression of matrix metalloproteinase-9 (MMP9) has been observed in asthmatic patients, yet the role of MMP9 genotype in determining asthma susceptibility remains unresolved. This study aimed to elucidate the contribution of MMP9 promoter rs3918242 genotype to asthma risk in Taiwan. A cohort comprising 453 non-asthmatic healthy controls and 198 asthmatic cases was assembled, and the MMP9 rs3918242 genotypes were determined using polymerase chain reaction-restriction fragment length polymorphism methodology. Our findings indicated that people carrying the variant CT or TT genotype of MMP9 rs3918242 did not demonstrate an elevated risk of asthma compared to wild-type CC carriers (odds ratio=1.28 and 1.72, 95% confidence interval=0.87-1.87 and 0.72-4.13; p=0.2417 and 0.3201, respectively). Furthermore, individuals carrying the T allele at MMP9 rs3918242 did not exhibit a higher risk of asthma than those carrying the C allele (odds ratio=1.31, 95% confidence interval=0.96-1.79, p=0.0869). Interestingly, a positive association was observed between MMP9 rs3918242 CT or TT genotypes and the severity of asthma symptoms among asthmatic patients (p=0.0035). Although the T allele at MMP9 rs3918242 was not associated with asthma risk, it may serve as a predictor for asthma symptom severity. These findings warrant validation in larger and more diverse populations to further elucidate the significance of MMP9 in asthma etiology.

Contribution of Matrix Metalloproteinase-2 Genotypes to Taiwan Pterygium Risk.

In the literature, the studies about the role of matrix metalloproteinase-2 (MMP-2) in pterygium diagnosis are mainly based on its protein expression. The role of MMP-2 variants has never been examined. The aim of this study was to examine the association of MMP-2 genotypes with pterygium risk. MMP-2 rs243865 and rs2285053 were genotyped in 140 pterygium cases and 280 non-pterygium controls by typical polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) genotyping technology. The genotypic frequency of MMP-2 rs243865 CC, CT and TT were 86.4%, 12.9% and 0.7% in the pterygium group and 81.1%, 17.1% and 1.8% in the non-pterygium group (p for trend=0.3389). The variant CT and TT carriers had a 0.70- and 0.38-fold pterygium risk (95%CI=0.39-1.26 and 0.04-3.25, p=0.2982 and 0.6686, respectively). As for MMP-2 rs2285053, the genotypic frequency of CC, CT and TT were 67.1%, 28.6% and 4.3% in the pterygium group, non-significantly different from those in non-pterygium group (p for trend=0.7081). The CT and TT carriers had a 0.88- and 0.71-fold pterygium risk (95%CI=0.56-1.38 and 0.27-1.88, p=0.6612 and 0.6456, respectively). The allelic analysis results showed that MMP-2 rs243865 variant T allele was not associated with pterygium risk (7.1% versus 10.4%, OR=0.67, 95%CI=0.39-1.13, p=0.1649). As for MMP-2 rs2285053, the T allele was not associated with pterygium risk either (18.6% versus 21.1%, OR=0.85, 95%CI=0.59-1.23, p=0.4136). The genotypes at MMP-2 rs243865 or rs2285053 played minor role in determining individual susceptibility for pterygium among Taiwanese.

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.

High Prevalence of MMP9 −1562C/T Gene Polymorphism in an Iranian Population of Neuromyelitis Optica, A Pilot Study

Expression of matrix metalloproteinases correlates to blood-brain barrier disruption in Neuromyelitis Optica disease (NMO). Matrix metalloproteinase-9 (MMP9) −1562C/T polymorphism which influences the transcriptional activity of this gene is considered to play a role in some neuroinflammatory diseases. In the present study, the possible association of MMP9 –1562C/T polymorphism in Iranian NMO patients is studied.Association of the mentioned gene polymorphism of MMP9 with NMO susceptibility was evaluated via genotyping of DNA extraction from the blood samples of unrelated Iranian subjects referred to AlZahra Hospital, Isfahan, Iran during 2017 to 2019.Frequency distribution of MMP9 genotypes has a significant relationship with NMO disease; in such a way that CT + TT genotypes was more seen in NMO patients.Altogether, Since the MMP9 is one of the potential target molecules for future alternative treatment, the result of this study should be taken into account for further research. However, more studies should carry out to confirm our results in larger populations and reveal the convoluted role of MMP9 in Devic's disease.

Significant Association of MMP2 Promoter Genotypes to Asthma Susceptibility in Taiwan

Matrix metalloproteinase 2 (MMP2) is reported to be overexpressed in asthma; however, its genotypic contribution to asthma is not well studied. Therefore, we examined the association of MMP2 genotypes with asthma risk among Taiwanese. One hundred and ninety-eight asthma patients and 453 non-asthmatic subjects were determined with respect to their MMP2 -1306 (rs243845) and -735 (rs2285053) genotypes. CT and TT at MMP2 rs243845 are 17.7% and 1.5% among asthma cases, whereas their presence in healthy subjects is at 28.1% and 2.4%, respectively (p for trend=0.0118). In detail, the CT genotype in MMP2 rs243845 was associated with a decreased asthma risk [adjusted odds ratio (OR)=0.57, 95% confidence interval (CI)=0.37-0.78, p=0.0040], and the T allele conferred a significantly lower asthma risk compared to the wild-type C allele (adjusted OR=0.55, 95%CI=0.43-0.77, p=0.0042). No significance was found for MMP2 rs2285053. The genotype of CT in MMP2 rs243845 may serve as a novel biomarker in determining susceptibility to asthma in Taiwan.

Association of Matrix Metalloproteinase-9 rs3918242 Promoter Genotypes With Colorectal Cancer Risk.

Matrix metalloproteinase-9 (MMP-9) is responsible for modifying extracellular components and plays a crucial role in the metastatic behavior of cancer. This study aimed at examining the role of MMP-9 rs3918242 genotypes on colorectal cancer (CRC) risk. A total of 362 CRC patients and 362 healthy subjects in Taiwan, were examined by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methodology. The MMP-9 rs3918242 TT genotype carriers had a slightly increased risk of CRC compared to CC carriers (p=0.1642, OR=1.88, 95% CI=0.84-4.16). Patients of CT/TT genotypes were on significantly higher risk of metastasis (p=0.0027) than those of CC genotype. No obvious association was found between MMP-9 genotype and CRC risk among ever-smokers, non-smokers, non-alcohol drinkers or alcohol drinkers. No significant correlation was observed between MMP-9 genotypic distributions with age, gender, tumor size or location. MMP-9 rs3918242 genotypes may interact with BMI to serve as a predictor for higher CRC risk, and independently as a predictor for metastasis.

Association study between matrix metalloproteinase-3 gene (MMP3) polymorphisms and ankylosing spondylitis susceptibility.

BackgroundAnkylosing spondylitis (AS) is the second most common cause of inflammatory arthritis worldwide affecting the axial skeleton. Single nucleotide polymorphisms (SNPs) of matrix metalloproteinase‐3 (MMP3) in the development of AS has few been investigated in Chinese population.MethodsA total of 362 patients with AS and 362 healthy controls were enrolled in the study. Five SNPs in MMP3 genotypes were identified by Agena MassARRAY. Chi‐squared tests and genetic model were used to evaluate associations.Resultsrs522616 had a significant risk of AS development compared to those with the TT genotype (p = 0.008). By multiple logistic regression models analysis, in codominant model, rs522616 CT genotypes also had a 1.44‐fold risk (95% CI = 1.06–1.96, p = 0.008) for AS development compared to those with TT genotypes. In recessive model, the CC genotypes was a significantly reduced AS risk for individuals with TT/CT genotype (OR = 0.64; 95% CI = 0.41–0.99, p = 0.040).ConclusionThe present study suggests that MMP3 rs522616 polymorphism is associated with AS susceptibility and MMP3 might be a potential diagnostic biomarker for AS. Further independent studies with larger cohorts are warranted to validate our findings in different populations.

Impact of Angiotensin-converting Enzyme and Matrix Metalloproteinase-3 Gene Polymorphisms on Risk for Developing Vascular Access Failure in Hemodialysis Patients - A Pilot Study.

For adequate hemodialysis, functional vascular access is obligatory. Neointimal hyperplasia (NIH) has a central role in stenosis and thrombosis development, which represent the most frequent causes of vascular access failure. Polymorphism of different genes that have a significant role in endothelial function may have an impact on NIH development. Therefore, the aim of our study is to determine the effect of angiotensin-converting enzyme (ACE) I/D and matrix metalloproteinase-3 (MMP3) 5A/6A polymorphism on risk for developing vascular access failure in hemodialysis patients. The study included 200 patients on regular hemodialysis at Nephrology Department, University Medical Center Zvezdara. Retrospective analysis included a collection of general and vascular access data from medical records. Genetic analysis was performed by using polymerase chain reaction-restriction fragment length polymorphism method (PCR-RFLP). Patients were divided into two groups: Group 1—patients who have never experienced vascular access failure and Group 2—patients who have at least one spontaneous vascular access failure. There was no difference in age, gender, hemodialysis vintage, main diagnosis, presence of hypertension, and diabetes mellitus between the two groups. There were no statistically significant differences in the frequencies of ACE and MMP3 genotypes between the two groups. Without statistical significance, it was found that homozygotes for I allele had two times higher risk for developing vascular access failure than homozygotes for D allele (OR 2.00; 95%CI: 0.727–5.503; P = 0.180). In addition, patients with 5A allele have 1.7 times higher risk for developing vascular access failure compared with patients without this allele (OR 1.745; 95% CI: 0.868–3.507; P = 0.118). Patients with vascular access failure do not have different genotype distribution regarding ACE gene and MMP3 gene polymorphism as compared with patients without vascular access failure. Still, homozygotes for I allele and homozygotes for 5A allele have higher risk for developing vascular access failure compared with other patients.

Analysis of genetic polymorphisms associated with intervertebral disc degeneration

Intervertebral disc degeneration (IVDD) is a common degenerative spinal condition. Recent studies have shown that the incidence of disc herniation and disc degeneration may be explained by genetic factors. In this study, we investigated the link between various polymorphic variants of the vitamin D receptor (VDR), matrix metalloproteinase 2 (MMP2), and insulin like growth factor 1 receptor (IGF1R) genes and IVDD in patients with IVDD, in Turkey. We examined and genotyped 199 patients with IVDD and 197 healthy individuals. Genomic DNA was isolated from the peripheral blood leukocytes of all participants, and analyzed using real-time PCR. Via melting curve analysis, VDR, MMP2, and IGF1R polymorphism variant distributions were determined. The patients with IVDD showed higher frequencies of the VDR ApaI A allele genotype as compared to the control group; however, there were no significant differences in the frequencies or allelic distributions of the IGF1R and MMP2 genotypes between the IVDD patients and the control group. The incidence of IVDD in these Turkish patients is correlated with the VDR ApaI gene polymorphism, but not with the IGF1R and MMP2 polymorphisms.

The Variants in the 3' Untranslated Region of the Matrix Metalloproteinase 9 Gene as Modulators of Treatment Outcome in Children with Asthma.

The maintaining of asthma control is difficult due to high variability in response to therapy among patients. Since matrix metalloproteinase 9 (MMP9) is implicated in inflammation and remodeling of asthmatic airways, it could be associated with adequate response to asthma therapy. The aim of this study was to investigate whether variants in 3' end of the MMP9 gene are associated with clinical phenotype and responsiveness to treatment in children with asthma. The study included 127 asthmatic children from Slovenia. Variants in the 3' end of the MMP9 gene were analyzed by direct DNA sequencing and the obtained results were correlated with clinical parameters. Two variants were detected, rs13925 and rs20544. For the variant rs20544, statistically significant difference in airway hyperresponsiveness (p = 0.011) and asthma control (p = 0.049) between genotypes was found. Patients with TT genotype had lower airway sensitivity, and after 12 months of treatment showed significant improvement in Asthma Control Test (ACT) scores compared to CC and CT genotype. For the variant rs13925, the association with lung function was observed. The carriers of A allele showed noticeable improvement of lung function after the first 6 months of treatment in comparison to the carriers of G allele (p = 0.046). The main finding of our study is the association of MMP9 genotypes rs20544 TT and rs13925 AA and AG with better asthma control, and indirectly better response to treatment. Based on these results, MMP9 deserves further research as a potential predictive biomarker for asthma.

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.

Does MMP-3 polymorphism have a role in the etiology of the posterior tibial tendinopathy?

Summary Background Several risk factors and systemic conditions have been proposed in the etiology of posterior tibial tendon (PTT) tendinopathy. However, many patients present PTT dysfunction without any of these characteristics. This suggests that there could be a genetic influence associated with posterior tibial tendinopathy. Objective The purpose of the present study was to investigate the association of the −1612 polymorphism in the promoter gene of matrix metalloproteinase 3 (MMP-3) and posterior tibial tendinopathy. Methods The study group included 68 women who presented with PTT dysfunction grade 2 or 3, and who underwent surgical treatment, with histopathological examination of the tendon and magnetic resonance imaging (MRI) confirming tendinopathy. The control group consisted of 100 asymptomatic women with an intact PTT on magnetic resonance imaging (MRI). Results There was no statistically significant difference between the study and the control groups with respect to the presence of the different MMP-3 alleles and genotypes (Chi-square p value > 0.05). The odds ratio analysis showed OR = 1.9, p = 0.31 for 5A/5A vs. 6A/6A and OR = 1.8, p = 0.29 for 5A/5A vs. 6A/5A. Conclusion The −1612 polymorphism of the promoter gene of MMP-3 is not solely associated with posterior tibial tendinopathy in the studied population. Level of evidence: 3

Association of MMP3 genotype with susceptibility to frozen shoulder: a case-control study in a Chinese Han population.

Genetic factors may play an important role in frozen shoulder etiology, which may involve matrix metalloproteinase-3 (MMP3) gene polymorphisms. In this study, we examined single nucleotide polymorphisms in MMP3 for their association with frozen shoulder susceptibility in a Chinese Han population. The rs591058, rs650108, and rs679620 polymorphisms in the MMP3 gene were genotyped in 112 subjects diagnosed as having frozen shoulder and in 143 healthy controls. rs650108 was found to be significantly associated with an increased risk of frozen shoulder. For other single nucleotide polymorphisms, no statistically significant associations with frozen shoulder were found. In conclusion, our data demonstrated that the MMP3 rs650108 variant was significantly associated with increased frozen shoulder susceptibility in a Chinese Han population.

Effects of obesity on the association between common variations in the TBX5 gene and matrix metalloproteinase 9 levels in Taiwanese

ObjectivesThe TBX5 gene, a member of the T-box family, is associated with congenital heart disease, electrocardiographic parameters, and development of atrial fibrillation in the general population. This study aimed to elucidate the role of TBX5 gene polymorphisms in metabolic and inflammatory profiles possibly linked to TBX5-related pathologies. Materials and MethodsA sample population of 597 individuals having routine health examinations was enrolled. Five tagging TBX5 single nucleotide polymorphisms (SNPs) were analyzed using polymerase chain reaction and restriction enzyme digestion or TaqMan SNP genotyping assays. Associations between genotypes/haplotypes and matrix metalloproteinase 9 (MMP9) levels were investigated using generalized linear model analysis. Interactions between each genotype/haplotype, MMP9 level, and obesity status were tested using two-way analysis of variance with Golden Helix SVS Win32 7.3.1 software. ResultsAfter adjusting for clinical covariates, TBX5 genotypes were found to be associated with MMP9 levels (p = 0.002 and p = 0.001 for rs4113925 and rs3825214, respectively) in a dominant inheritance model. Haplotype analysis using three tag SNPs (rs11067101, rs1247973, and rs3825214) revealed a significant association between TBX5 haplotype GCG and MMP9 levels (uncorrected p = 0.0093 and the corrected false discovery rate p = 0.0435). Multivariate analysis identified that SNP rs3825214, in addition to the MMP9 and E-selectin genotypes, was independently associated with MMP9 levels (p < 0.001). Using a dominant inheritance model, subgroup and interaction analysis showed associations between the rs4113925, rs3825214, and MMP9 levels only in nonobese individuals (p = 1.04 × 10−4 and p = 7.11 × 10−5, respectively; interaction p = 0.009 and 0.018, respectively). Subgroup analysis showed a borderline significant association between haplotype GCG and MMP9 levels (uncorrected p = 0.020 and corrected false discovery rate p = 0.073), but with no evidence of interaction. ConclusionTBX5 genotypes/haplotypes are independently associated with MMP9 in Taiwanese individuals and occur predominantly in nonobese people. These associations may broaden our understanding of the mechanism underlying T-box family gene activity and related cardiovascular pathologies.

Prognostic impact of polymorphism of matrix metalloproteinase-2 and metalloproteinase tissue inhibitor-2 promoters in breast cancer in Tunisia: case-control study.

Matrix metalloproteinases (MMPs) are proteolytic enzymes that play important roles in tumor invasion and metastasis by degrading extracellular matrix components. Genetic variations in promoter regions of MMP genes, affecting their expression, have been associated with susceptibility to cancers. The aim of this study was to investigate the susceptibility and prognostic implications of the matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of metalloproteinase-2 (TIMP-2) polymorphism in Tunisian breast cancer patients. MMP-2 genotypes were determined by real-time polymerase chain reaction (RT-PCR), and TIMP-2 genotypes were identified using a PCR-restriction fragment length polymorphism (RFLP) method in 210 breast cancer patients and 250 frequency-matched control women. Association of the clinicopathological parameters and the genetic markers with risk of breast cancer was assessed using univariate analyses. We found that the variant MMP-2 genotype (-1306CT or TT) was associated with substantially reduced risk of breast cancer [odds ratio (OR), 0.49; 95 % confidence interval (95 % CI), 0.033-0.73], compared with the CC genotype. For TIMP-2, a moderately reduced risk of the cancer (OR, 0.57; 95 % CI, 0.37-0.87) was also associated with the variant allele (-418GC or CC), compared with the GG common allele. Furthermore, polymorphisms in both genes seem to have additive effects and the highest risk for breast cancer has been observed in those with MMP-2 CC genotype and TIMP-2 GC or CC genotype (p = 0.006). A significant association was also found between the CC genotype and the aggressive forms of breast cancer as defined by advanced stages at the time of diagnosis and metastasis. This is the first report on the association of MMP-2 and TIMP-2 gene polymorphisms in breast cancer in Tunisian population. Our results suggest that the presence of the variant allele in the promoter of MMP-2 or TIMP-2 may be a protective factor for the development of breast cancer.

Assessment of the role of matrix metalloproteinase-3 gene polymorphism in the development of chronic heart failure

To study the impact of a polymorphic variant of the matrix metalloproteinase-3 (MMP-3) gene on the development and course of chronic heart failure (CHF) in patients with coronary heart disease. A total of 277 patients with New York Heart Association (NYHA) Functional Class (FC) II-IV CHF were examined. MMP-3 -1171 5A/6A genetic polymorphism was studied by polymerase chain reaction. A control group included 136 patients (mean age 53.6 ± 4.8 years) with no signs of cardiovascular diseases, as evidenced by the examination. The frequency of the 5A allele and the 5A/5A genotype of the 1171 5A/6A polymorphic locus in the MMP-3 gene proved to be higher in the patients with CHF than that in the control group. Thus, the variability of the 5A allele (odds ratio (OR), 1.39; 95% confidence interval (CI): 1.033 to 1.869; p = 0.03) and the 5A/5A genotype (OR, 2.15; 95% CI: 1.131 to 4.070; p = 0.02) was associated with increased risk for CHF. There were significant differences in the frequency of MMP-3 alleles and genotypes in relation to FC of CHF. The frequency of the 5A/5A genotype was substantially higher in the patients with NYHA FC IV CHF than that in those with NYHA FC II CHF (32.8% versus 15.2%; p = 0.039). The frequency of the 5A allele was significantly higher in the patients with NYHA FC IV CHF than that in those with NYHA FC II CHF (55.5% and 39.3%; respectively; p = 0.019). Thus, the carriage of the 5A allele and the 5A/5A genotype of the 1171 5A/6A polymorphic locus in the MMP-3 gene is a risk factor of severe CHF. The determination of MMP-3 -1171 5A/6A polymorphism may be recommended for the early prediction of a risk for the development and severe course of CHF.

Matrix Metalloproteinase-9 Level and Gene Polymorphism in Sleep Disordered Breathing Patients with or without Cardiovascular Disorders.

Obstructive sleep apnea syndrome (OSAS) is associated with increased cardiovascular morbidity and mortality. We aimed to investigate the matrix metalloproteinase-9 (MMP-9) level and MMP-9 gene polymorphism in sleep apnea patients with or without cardiovascular disease. Case-control study. Two hundred nine patients [Mean age (±SD), 47 (±12) yrs; M/F, 170/39] diagnosed with sleep-disordered breathing were included in the study. Serum MMP-9 level was performed using enzyme-linked immunosorbant assay (ELISA) and MMP-9 gene polymorphism with polymerase chain reaction-restriction fragment length polymorphism. We divided the patient group into two subgroups: (1) patients with confirmed cardiovascular disease, i.e. CV-P Group and (2) patients without cardiovascular disease, CV-N Group. We compared all parameters between the two groups. There were 56 OSAS patients with cardiovascular disorder (CV-positive group) and 153 OSAS patients without cardiovascular disorder (CV-negative group). CC, CT and TT genotype distributions between groups were similar [31 (55%), 25 (45%), 0 (0%) vs 88 (57%), 61 (40%), 4 (3%); respectively, p>0.05]. MMP-9 level was significantly higher in CV-P patients (442.7±139.3 pg/mL) than in CV-N patients (364.4±165.0 pg/mL; p=0.0018). Our results showed that the presence of MMP-9 polymorphism was not associated with cardiovascular disease. MMP-9 level was higher in OSAS patients with cardiovascular disorders than without cardiovascular disorders. Finally, MMP-9 genotype was not associated with serum MMP-9 levels.

MMP-9 -1562 Promoter Polymorphism Associated with Gastric Cancer Risk in Females.

Background/Aims: C to T transition at the matrix metalloproteinase-9 (MMP-9) promoter site -1562 abolishes a binding site of a putative transcription repressor protein to the C allelic promoter. The aim of this study is to elucidate the significance of MMP-9 genotypes in clinicopathological manifestations of gastric cancer. Methodology: We conducted a case-control study based on previously stored peripheral blood samples from 263 gastric cancer patients and 354 controls. MMP-9 genotyping was analyzed by PCR-RFLP method. Stratified analysis, logistic regression and Cox proportional hazards analysis were used to evaluate the associations between polymorphisms and gastric cancer development, invasiveness, and survival. Results: There was significant correlation between female patients with MMP-9 -1562 C/T or T/T genotype and higher risk of gastric cancer (OR=2.12, p=0.02). On stratified analysis, only elderly females with T allele had higher risk of gastric cancer (OR=2.64, p=0.04). On Cox proportional hazards analysis, serosal invasion (adjusted HR=3.47, p<0.001) and lymph node metastasis (adjusted HR=2.31, p=0.003), but not MMP-9 polymorphism, were independent prognostic factors for survival. Conclusions: MMP-9 -1562 promoter polymorphism with T allele may be used as a marker to predict gastric cancer development in female subjects, especially in the elderly.