MMP-9 Polymorphisms Research Articles

Influence of metalloproteinase-3 (-1171 5A>6A) polymorphism on periportal fibrosis in patients with schistosomiasis mansoni, Pernambuco, Brazil

In schistosomiasis mansoni (SM), periportal fibrosis (PPF) arises due to an inflammatory response exacerbated by parasite eggs in the intrahepatic portal space, culminating in the deposition of collagen and extracellular matrix proteins. This fibrosis results from a remodeling process of the extracellular matrix, in which metalloproteinases play a significant role. The study evaluated the association between MMP-3 polymorphism (-1171 5A>6A) (rs 3025058) and sociodemographic factors with PPF in individuals with SM. This is an analytical cross-sectional study involving 242 individuals infected with S. mansoni, of these 122 were diagnosed with hepatosplenic form (HS) and 119 hepatointestinal form (HI), all from the state of Pernambuco, Brazil. Polymerase chain reaction with restriction enzyme digestion (Psyl) was used to determine the MMP-3 polymorphism (-1171 5A>6A). There was a significant association between the male gender and the HS form (OR = 1.7623 95% CI [1.0481–2.9631]; p-value = 0.0439) as well as individuals aged over 41, also had a greater chance of developing this clinical form of the disease (OR = 2.8299; 95% CI [1.5211–5.2650]; p-value = 0.0014), with greater emphasis on individuals over 61 years old (OR= 8.5541; 95% CI [3.6895–19.8326], p-value= 0.0000). There was no statistically significant association between the MMP-3 polymorphism (-1171 5A>6A) between the clinical groups (5A6A CI [0.7144–1.9879] p-value 0.5882 5A5A CI [0.0912–2.9231] p-value 0.7331 5A6A / 5A5A CI [0.6904–1.8937] p-value 0.6949). In conclusion, the results showed no association between the MMP-3 polymorphism (-1171 5A>6A) and the development of PPF. In addition, males, and age over 41 were predictive factors for the HS form of the disease in this Brazilian population.

Preliminary investigation of MMP8 (rs11225395) and MMP9 (rs3787268) polymorphisms association with breast cancer risk in pashtun women of Pakistan.

Single Nucleotide polymorphisms (SNPs) in MMP8 and MMP9 have been widely associated with breast cancer risk in different ethnicities with inconsistent results. There is no such study conducted so far in the Pashtun population of Khyber Pakhtunkhwa, Pakistan. Therefore, this study was conducted to check MMP8 (rs11225395) and MMP9 (rs3787268) polymorphism with breast cancer risk in the selected population. This study, consisting of 300 breast cancer patients and 168 gender and age-matched healthy controls was subjected to confirm MMP8 and MMP9 polymorphisms. Clinicopathological data and blood samples were taken from all the participants. DNA was extracted and SNPs were confirmed using the T-ARMS-PCR protocol. Based on our study results, significant associations were observed between the MMP8 rs11225395 risk allele (G) and increased breast cancer risk, with the G allele frequency higher in patients (65%) compared to controls (51%) (OR = 1.752, 95% CI = 1.423-3.662, p = 0.002). Genotypes GG (OR = 4.218, p = 0.005) and AG (OR = 7.286, p = 0.0001) of MMP8 rs11225395 were also significantly associated with elevated breast cancer risk. Similarly, MMP9 rs3787268 exhibited a higher frequency of the risk allele (A) in breast cancer cases (81%) compared to controls (41%), correlating strongly with increased risk (OR = 6.320, p = 0.0001). Genotypes AA (OR = 14.500, p = 0.0001) and AG (OR = 2.429, p = 0.077) of MMP9 rs3787268 containing the risk allele showed significant associations with heightened breast cancer risk. Subgroup analyses based on age, disease progression, tumor size, and grade revealed noteworthy associations for both MMP8 rs11225395 and MMP9 rs3787268. MMP8 rs11225395 genotypes displayed significant correlations with age (p = 0.066), disease progression (p = 0.0001), larger tumor size (p = 0.005), and higher tumor grade (p = 0.006). Similarly, MMP9 rs3787268 genotypes were significantly associated with age (p = 0.001), disease progression (p = 0.010), larger tumor size (p = 0.018), and higher tumor grade (p = 0.037). Logistic regression analyses further underscored these genetic variants' potential role as biomarkers in breast cancer, particularly in relation to specific hormone receptor statuses such as estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) positivity. The results revealed significant associations between the mutant alleles and genotypes of MMP8 (rs11225395) and MMP9 (rs3787268) with increased breast cancer risk in the Pashtun population of Khyber Pakhtunkhwa, Pakistan. However, more investigation will be required on large data sets to confirm the selected SNPs and other SNPs in the selected and other related genes with the risk of breast cancer.

MMP1 and SOD2 genes polymorphism in occupational diseases pathogenesis in workers of mining and processing enterprises

Introduction. Vibration disease (VD) is occupational disease that develops with prolonged exposure to industrial vibration. VD is one of the most common occupational pathologies. This disease is characterized by pathogenetic mechanisms complexity, polymorphic symptoms, chronic course, therapeutic resistance, and often leads to disability of patients. As a rule, changes in the cardiovascular and nervous systems, musculoskeletal system and metabolic processes are observed with VD. The aim of study was to find associations of polymorphic variants rs1799750 of MMP1 and rs4880 of SOD2 genes with vibration disease. Materials and methods. 73 people with various forms of VB were examined. The control group consisted of 73 people who were not exposed to vibration in their professional activities. The distribution of polymorphic loci rs1799750 of MMP1 gene and rs4880 of SOD2 gene was studied. Statistical analysis was performed using the IBM SPSS Statistica v.21 and Microsoft Excel software packages. Results. It was revealed that *d allele of rs1799750 of MMP1 gene associated with VD (p=0.046), but its frequency is lower among VD patients with sensorineural hearing loss compared to VD patients without this syndrome (p=0.035). The frequency of *T/*T genotype and the *T allele of rs4880 is increased among patients with peripheral angiodystonic syndrome of VD. Limitations. The limitations of this work include the small sample size and the fact that the study participants from the control sample work at a different enterprise, which does not allow us to exclude the influence of other environmental factors, but allows us to consider them as a reference population. Conclusion. Thus, we were unable to identify a direct association of the studied genotypes with VD, but the association with peripheral angiodystonic syndrome suggests that these polymorphisms affect the pathogenesis of VD.

The Effects of MMP3 (rs679620) and VDR (rs731236) Gene Polymorphisms on Dental Caries: A Pilot Study.

Caries formation is a process affected by various factors. Studies have shown that genetic factors also play a role in caries formation. The aim of our study is to examine the effects of matrix metalloproteinase (MMP)3 (rs679620) and vitamin D receptor (VDR) (rs731236) gene polymorphisms on caries formation. Following routine oral examinations in individuals aged between 20 and 44 years, the diagnosis was made according to the decayed, missing, and filled teeth (DMFT) index, and experimental group was defined as "high caries risk" (DMFT ≥ 14, n = 28), and the control group as "no caries" (DMFT = 0, n = 28). Plaque index and bleeding on probing were measured from participants with a detailed anamnesis. Periodontally healthy individuals with less than 10% bleeding on probing were included in the study (n = 56). After DNA isolation from blood samples taken from the participants, the genotyping of MMP3 (rs679620) and VDR (rs731236) gene polymorphisms were determined using the real-time polymerase chain reaction technique. Data were analyzed with IBM SPSS V23.0. Data distribution was evaluated with Kolmogorov-Smirnov's test. Pearson's chi-square test was used to compare categorical data according to groups. The results were evaluated using a significance level of p < 0.05. Regarding MMP3 and VDR gene polymorphisms, there was a statistically significant difference between the groups in terms of MMP3 (rs679620) (p < 0.001). There was no statistically significant difference between the VDR (rs731236) genotype distributions of the groups (p = 0.659). Within the limits of this study, MMP3 rs679620 gene polymorphism may have an effect on caries formation.

The Association of MMP-2, MMP-9, and MMP-13 Gene Polymorphisms With Knee Osteoarthritis in the Greek Population.

Introduction Primary knee osteoarthritis (OA) is a multifactorial degenerative joint disorder characterized by articular cartilage degradation. Matrix metalloproteinases (MMPs) have been reported to play a vital role in OA pathogenesis, significantly contributing to extracellular matrix (ECM) catabolism. The purpose of this study is to investigate the association of MMP-2 -1575G/A (rs243866), MMP-9 836A/G (rs17576), and MMP-13 -77A/G (rs2252070) gene polymorphisms with knee OA in the Greek population. Methods One hundred patients (24% males, mean age: 68.3 years) with primary knee OA were included in the study along with 100 controls (47% males, mean age: 65.2 years). Genotypes were identified through polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) technique. Allelic and genotypic frequencies were compared between patients and controls. Results The MMP-13 -77A/G polymorphism was significantly associated with knee OA in the crude analysis (P = 0.008). After binary logistic regression analysis, the dominant model of the MMP-13-77A/G (AG + GG versus AA) was found to be associated with increased risk for knee OA (odds ratio (OR) = 2.290, 95% confidence interval (95%CI) = 1.059-4.949, P= 0.035).Compared to the A allele, the G allele in the MMP-13rs2252070 locus was a predictive factor for knee OA (OR = 2.351, 95%CI = 1.134-4.874, P= 0.022). No significant associations were detected for the MMP-2 -1575G/A and MMP-9 836A/G polymorphisms (P > 0.05). Conclusions The present study shows that the MMP-2 -1575G/A and MMP-9 836A/G polymorphisms are not significantly associated with primary knee OA in the Greek population. The MMP-13 -77A/G was found to be a significant risk factor for knee OA in the Greek population. Additional research is needed to verify this association in larger and different populations, in different joints, to elucidate the role of this single nucleotide polymorphism (SNP) in OA pathogenesis.

Contribution of Matrix Metalloproteinase-2 and Matrix Metalloproteinase-9 to Upper Tract Urothelial Cancer Risk in Taiwan.

Matrix metalloproteinase (MMP)-2 and -9, which degrade type IV collagen, are linked to cancer invasion and metastasis. Gene polymorphisms in MMP-2 and MMP-9 can influence their function, impacting cancer development and progression. This study analyzed the association between polymorphisms MMP-2 rs243865 (C-1306T), rs2285053 (C-735T), and MMP-9 rs3918242 (C-1562T) with serum concentrations of these enzymes in upper tract urothelial cancer (UTUC) patients. We conducted a case-control study with 218 UTUC patients and 580 healthy individuals in Taiwan. Genotyping was performed using PCR/RFLP on DNA from blood samples, and MMP-2 and MMP-9 serum levels and mRNA expressions in 30 UTUC patients were measured using ELISA and real-time PCR. Statistical analysis showed that MMP-2 rs2285053 and MMP-9 rs3918242 genotypes were differently distributed between UTUC patients and controls (p = 0.0199 and 0.0020). The MMP-2 rs2285053 TT genotype was associated with higher UTUC risk compared to the CC genotype (OR = 2.20, p = 0.0190). Similarly, MMP-9 rs3918242 CT and TT genotypes were linked to increased UTUC risk (OR = 1.51 and 2.92, p = 0.0272 and 0.0054). In UTUC patients, TT carriers of MMP-2 rs2285053 and MMP-9 rs3918242 showed higher mRNA and protein levels (p < 0.01). These findings suggest that MMP-2 rs2285053 and MMP-9 rs3918242 genotypes are significant markers for UTUC risk and metastasis in Taiwan.

Predicting the risk of developing vibration disease and vegetative-sensory polyneuropathy under vibration exposure using analysis of candidate gene polymorphism

In this study, we investigated the association of IL-6 (rs1800795), TNF-α (rs361525), IL-1β (rs16944), MMP-1 (rs1799750) and SOD2 (rs4880) gene polymorphisms with the risk of developing vibration disease (VD) and autonomic sensory polyneuropathy (ASPN). We examined 45 patients with VB, 10 patients with ASPN and 76 people who were not exposed to vibration in their professional activities. Polymorphic gene variants were determined using a real-time polymerase chain reaction. The polymorphic variant rs16944 of the IL-1β gene was established to carry both the G allele (p = 0.027) and the homozygous G/G genotype (p = 0.015) with elevated frequency in the group of patients with VD relative to the control group. Allele A of the rs361525 polymorphic variant of the TNF-α gene was more common in patients with ASPN as compared to controls, (p = 0.047). Statistically significant differences in polymorphic variants rs1800795 of the IL-6 gene, rs1799750 of the MMP-1 gene and rs4880 of the SOD2 gene were not found in both groups of patients as compared to the control group. However, when comparing groups of patients with each other, we established that the G allele of the polymorphic variant rs1800795 of the IL-6 gene was more often recorded in patients with ASPN (p = 0.032). The results obtained by examining the patients with VD and ASPN made it possible to establish that the rs361525 polymorphic variant of the TNF-α gene is associated with an elevated risk of developing ASPN, while carriers of the homozygous genotype G/G of the rs16944 polymorphic variant of the IL-1β gene have a high prognostic risk of developing VD. Polymorphic variants of the IL-1β and TNF-α genes can be considered probable molecular genetic predictors of VD and ASPN.

Прогнозирование риска развития вибрационной болезни и вегетативно-сенсорной полинейропатии при вибрационном воздействии с исполь-зованием анализа полиморфизма кандидатных генов

In this study, we investigated the association of IL-6 (rs1800795), TNF-α (rs361525), IL-1β (rs16944), MMP-1 (rs1799750) and SOD2 (rs4880) gene polymorphisms with the risk of developing vibration disease (VD) and autonomic sensory polyneuropathy (ASPN). We examined 45 patients with VB, 10 patients with ASPN and 76 people who were not exposed to vibration in their professional activities. Polymorphic gene variants were determined using a real-time polymerase chain reaction. The polymorphic variant rs16944 of the IL-1β gene was established to carry both the G allele (p = 0.027) and the homozygous G/G genotype (p = 0.015) with elevated frequency in the group of patients with VD relative to the control group. Allele A of the rs361525 polymorphic variant of the TNF-α gene was more common in patients with ASPN as compared to controls, (p = 0.047). Statistically significant differences in polymorphic variants rs1800795 of the IL-6 gene, rs1799750 of the MMP-1 gene and rs4880 of the SOD2 gene were not found in both groups of patients as compared to the control group. However, when comparing groups of patients with each other, we established that the G allele of the polymorphic variant rs1800795 of the IL-6 gene was more often recorded in patients with ASPN (p = 0.032). The results obtained by examining the patients with VD and ASPN made it possible to establish that the rs361525 polymorphic variant of the TNF-α gene is associated with an elevated risk of developing ASPN, while carriers of the homozygous genotype G/G of the rs16944 polymorphic variant of the IL-1β gene have a high prognostic risk of developing VD. Polymorphic variants of the IL-1β and TNF-α genes can be considered probable molecular genetic predictors of VD and ASPN.

SNP-SNP positive interaction between MMP2 and MMP12 increases the risk of COPD.

Determining SNP-SNP interaction of the disease has become important for further investigation of pathogenesis and experimental research. Although many studies have been published on the effect of MMPs gene polymorphisms on chronic obstructive pulmonary disease (COPD), there is a lack of information on SNP-SNP and SNP-environment interactions. This study aimed to investigate the interaction between the polymorphisms of MMP1, MMP2, MMP9 and MMP12 genes and its combined effect with smoking on the risk of developing COPD. Totally 181 COPD patients and 292 healthy individuals were involved. Blood samples from the participants were tested for genotyping and data were collected through questionnaires. Genotyping was performed with nested allele-specific polymerase chain reaction (AS-PCR) and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). SNP-SNP and SNP-environment interactions were investigated using multifactor dimensionality reduction and logistic regression analysis. The result showed that participants with high nicotine dependence and heavy smokers had a higher risk of COPD than non-smokers. Also, G/G genotype (cOR = 5.83; 95% CI, 1.19-28.4, p = 0.029) of MMP2 rs243864 and T/T genotype (cOR = 1.79; 95% CI, 1.16-2.76, p = 0.008) of MMP12 rs652438 independently contributes to the susceptibility of COPD. For SNP-SNP interaction, the positive interaction between rs243864 G/G genotype of MMP2 and rs652438 T/T genotype of MMP12 was found, and the combination of risk genotypes has a high risk of COPD (OR = 12.92; 95% CI, 1.46-114.4, p = 0.021). Moreover, the combination of T/T genotype of MMP12 rs652438 and smoking-related factors increases the risk of COPD approximately 4.5 to 6-fold. The results suggests that there is a combination of MMP2, MMP12, and smoking-related factors may increase the risk of developing COPD.

MMP-1, MMP-8, and MMP-13 Gene Polymorphisms and Haplotype Is a Risk Factor for Dupuytren Contracture: A Case-Control Study.

There is an increased tissue expression of matrix metalloproteinases (MMPs) on Dupuytren contracture (DC). Genetic polymorphisms (single nucleotide polymorphism [SNPs]) in genes of these enzymes may individually influence these transcriptions. Haplotype analysis, which is the observation of a group of alleles, could be more useful to identify the association between SNPs and DC. The purpose of this study was to evaluate the influence of MMP-1 g.-1607 G>GG (rs1799750), MMP-8 g.-799 C>T (rs11225395), and MMP-13 g.-77 A>G (rs2252070) SNPs individually and in haplotype on DC. A total of 60 patients with a clinical diagnosis of DC were evaluated and matched, according to age and gender, with the control group of 100 patients without this clinical diagnosis. Genomic DNA was extracted from saliva samples, and genotypes were obtained by polymerase chain reaction-restriction fragment length polymorphism. Statistical analysis of the results included Mann-Whitney U test, Chi-squared test, and PHASE and R software, with a significance level of 5%. The 3 SNPs studied showed significant differences in allele and genotype frequencies between the groups: 2G in MMP-1 (P = .018; odds ratio [OR] 1.80 (95% confidence interval [CI], 1.13-2.88)), T in MMP-8 (P = .015; OR 0.53 (95% CI, 0.33-0.88)), and A in MMP-13 (rs2252070) SNPs (P = .040, OR 0.54 (95% CI, 0.33-0.90)) are risk alleles. The global haplotype analysis indicated a significant difference between both groups. In conclusion, MMP-1 g.-1607 G>GG (rs1799750), MMP-8 g.-799 C>T (rs11225395), and MMP-13 g.-77 A>G (rs2252070) SNPs, individually and in haplotype, are a risk factor for DC, indicating that these SNPs may be a potential diagnostic and prognostic factor for DC.

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.

Associations of the rs1132896 polymorphism of the matrix metalloproteinase type 2 gene with the development of acute cerebrovascular accident: prospective case–control study

BACKGROUND: The study focused on the identification of new genetic predictors in the Russian population, particularly associations of the rs1132896 polymorphism of the matrix metalloproteinase type 2 gene (MMP-2) with the development of acute cerebrovascular accident (ACVA).&#x0D; OBJECTIVE: To investigate the relationship of rs1132896 gene MMP-2 polymorphisms with ACVA development.&#x0D; MATERIALS AND METHODS: The prospective, case–control study enrolled 318 patients with stroke (main group) and 323 controls (control group). The age of the patients in the main group ranged from 32 to 69 [57.0; 51.0–62.0] years. In the control group, the age of the patients ranged from 37 to 68 [55.0; 51.0–62.0] years, which was comparable to that of the main group. Sexual dimorphism was as follows: 191 men (age [56.5; 51.0–62.0]) and 127 women (age [57.0; 51.0–62.0]). The sex composition in the control group corresponded to that in the main group: 214 men (age [55.0; 51.0–62.0]) and 109 women (age [55.0; 51.0–62.0]). The main group underwent clinical examination, computed tomography of the brain, electrocardiography, echocardioscopy, duplex ultrasound scanning of the extracranial brachiocephalic arteries, 24-h monitoring of blood pressure and heart rate, and analysis of the blood coagulation system. Molecular genetic research was conducted at a branch of the Institute of Cytology and Genetics of the Siberian Branch of RAS (Novosibirsk). All patients provided written informed consent to participate voluntarily in the study. The duration of the study was 3 years, starting in 2019. The primary study endpoint was a diagnosis of stroke, verification of concomitant cardiovascular pathology, and risk factors for stroke development. Statistical processing of the results was performed using SPSS Statistics v. 22 (IBM Corp., USA) and MedCalc 22.006 (Microsoft, USA). When comparing extended variables, the Mann–Whitney U-test was used. Discrete values were compared using Pearson’s χ2 test.&#x0D; RESULTS: When analyzing statistical significance, a predominance of the homozygous CC genotype was recorded in the group of male patients with stroke: n=24 (12.6%) vs n=20 (9.3%; p=0.0324). In addition, in the group of women, a statistically significant predominance of the heterozygous CG genotype was noted in women with stroke: n=67 (52.8%) vs n=42 (38.5%; p=0.0420).&#x0D; CONCLUSION: The homozygous CC genotype in men and the heterozygous CG genotype in women may be genetic predictors of the development of ACVA. The study of genetic factors in the development of ACVA is necessary to create a personalized approach to patient management at the outpatient and inpatient stages of medical care.

Association of MMP3, MMP14, and MMP25 gene polymorphisms with cerebral stroke risk: a case-control study

BackgroundCerebral stroke (CS) is the leading cause of death in China, and a complex disease caused by both alterable risk factors and genetic factors. This study intended to investigate the association of MMP3, MMP14, and MMP25 single nucleotide polymorphisms (SNPs) with CS risk in a Chinese Han population.MethodsA total of 1,348 Han Chinese were recruited in this case-control study. Four candidate loci including rs520540 A/G and rs679620 T/C of MMP3, rs2236302 G/C of MMP14, and rs10431961 T/C of MMP25 were successfully screened. The correlation between the four SNPs and CS risk was assessed by logistic regression analysis. The results were analyzed by false-positive report probability (FPRP) for chance or significance. The interactions between four SNPs associated with CS risk were assessed by multifactor dimensionality reduction (MDR).Resultsrs520540 A/G and rs679620 C/T SNP in MMP3 were associated with risk of CS in allele, codominant, dominant and log-additive models. Ischemic stroke risk were significantly lower in carriers with rs520540-A allele and rs679620-T allele than those with G/G or C/C genotypes. However, rs520540-A allele and rs679620-T allele were associated with higher risk of hemorrhagic stroke. Stratified analysis showed that these two SNPs were associated with reduced risk of CS in aged < 55 years, non-smoking and non-drinking participants, and rs679620 SNP also reduced CS risk in male participants. The levels of uric acid, high-density lipoprotein cholesterol, and eosinophil were different among patients with different genotypes of rs520540 and rs679620. No statistically significant association was found between MMP14 rs2236302 G/C or MMP25 rs10431961 T/C with CS even after stratification by stroke subtypes, age, gender as well as smoking and drinking conditions in all the genetic models.ConclusionMMP3 rs520540 A/G and rs679620 C/T polymorphisms were associated with CS risk in the Chinese Han population, which provides useful information for the prevention and diagnosis of CS.

Association of MMP2 and MMP9 gene polymorphisms with nonsyndromic cleft lip/palate in an Iranian population.

Cleft lip/palate (CL/P) is a prevalent congenital disorder. Matrix metalloproteinases (MMPs) play a role in palatogenesis and have been proposed to be associated with nonsyndromic CL/P development. This study aimed to examine the association of MMP2 (rs243866) and MMP9 (rs3918242) gene polymorphism with nonsyndromic CL/P in an Iranian population. Blood samples were collected from 120 nonsyndromic CL/P patients and 140 healthy newborns in this case-control study. DNA extraction was performed by the salting-out method, and the samples underwent polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP), using Pag and SphI enzymes, for genotyping MMP2 and MMP9 gene polymorphisms. Statistical analysis was performed with SPSS 11.5. Univariate and multivariate logistic regression models were used to calculate the odds ratios and 95% confidence intervals (CIs). The level of statistical significance was set at P<0.05. No significant association was found between MMP2 gene polymorphism and nonsyndromic CL/P. However, the MMP9 gene polymorphism had a significant association with nonsyndromic CL/P, with a higher prevalence of the T allele and TT genotype in the case group than the control group. This study indicated a potential link between MMP9 gene polymorphism and nonsyndromic CL/P in an Iranian population. Future investigations with greater sample diversity and larger sample sizes are required to obtain more comprehensive and robust evidence. In-depth analyses and studies involving different ethnic groups can further enhance our understanding of the genetic underpinnings of CL/P.

Evaluation of matrix metalloproteinase-1, -2, -3, -7, and -13 gene polymorphisms in patients with chronic periodontitis and healthy controls.

The current study aimed to investigate the association of matrix metalloproteinase- (MMP-) 1, -2, -3, -7, and -13 gene polymorphisms with chronic periodontitis (CP) in an Iranian population. In this case-control study, 87 subjects with CP and 89 periodontally healthy subjects were allocated to case and control groups, respectively. Subjects' venous blood samples (5cc) were collected, and DNA extraction was performed. A spectrophotometer was utilized to assess the concentration of extracted DNAs. The desired gene polymorphisms were examined using restriction fragment length polymorphism polymerase chain reaction (RFLP-PCR) followed by electrophoresis. Statistical analyses were done using the Pearson Chi-Square test, odds ratio, and t-Test using SPSS Version 28. The MMP-1 (-1607 1G/2G) rs1799750, MMP-3 (-1171 5A/6A) rs3025058, and MMP-7 (-181 A/G) rs11568818 gene polymorphisms significantly differed between case and control groups (PV = 0.019, 0.007, and 0.028, respectively). In contrast, the gene polymorphisms of MMP-2 (-1306 C/T) rs243865 and MMP-13 (-77 A/G) rs2252070 did not make a significant difference. Regarding allele frequencies, the presence of the 2G allele in the MMP-1 (-1607) rs1799750 genotype increased the CP susceptibility significantly, while subjects with the 6A allele in their MMP-3 (-1171) rs3025058 genotype showed significantly lower susceptibility to CP (PV = 0.008 and < 0.001, respectively). In the studied population, gene polymorphisms in the DNA sequences of MMP-1 (-1607 1G/2G) rs1799750, MMP-3 (-1171 5A/6A) rs3025058, and MMP-7 (-181 A/G) rs11568818 may have impacts on CP incidence. Clinicians should be cautious about the association between MMP-1, MMP-3, and MMP-7 gene polymorphisms and the incidence of chronic periodontitis during periodontal treatment planning.

Association of MMP1 gene polymorphisms with breast cancer risk: A narrative review.

Breast cancer is a multifactorial malignancy with different clinicopathological and molecular characteristics. It is the most frequent cancer in women in terms of both incidence and mortality. Matrix metallopeptidase 1 or MMP1 is a zinc-dependent endopeptidase associated with several physiological processes through the modification of the extracellular matrix and tumor microenvironment. However, previous results did not suggest any concluding remarks on the correlation between MMP1 gene polymorphisms and the risk of breast cancer. A comprehensive literature search was performed in PubMed database to retrieve relevant articles and extract data from suitable ones. The literature written only in English was selected for this review. A total of 26 articles were included in the present narrative review. From the available studies, it is observed that MMP1 is upregulated in breast cancer tissues and found to be correlated with metastasis and invasion. The expression of MMP1 gene is mediated by numerous factors, including polymorphisms which act as a potential risk factor for the progression of breast cancer. To establish the correlation between genetic polymorphisms in MMP1 and the risk of breast cancer, several case-control studies, as well as genetic analyses, have been carried out in different ethnicities. The association of genetic polymorphisms in MMP1 with the risk and survival of breast cancer in different populations has been reviewed in this study. Moreover, the structural domain of MMP1 and the role of MMP1 in breast cancer metastasis and invasion are also discussed which will help to understand the potential impact of MMP1 as a genetic biomarker. This review provides an overview of the MMP1 gene polymorphisms in breast cancer. However, we recommend future studies concentrating on combined analysis of multiple SNPs, gene-gene interactions, and analysis of epigenetics, proteomics, and posttranscriptional modifications that will provide the best outcome.

A potential relationship between MMP-9 rs2250889 and ischemic stroke susceptibility.

Ischemic stroke (IS), a serious cerebrovascular disease, greatly affects people's health and life. Genetic factors are indispensable for the occurrence of IS. As a biomarker for IS, the MMP-9 gene is widely involved in the pathophysiological process of IS. This study attempts to find out the relationship between MMP-9 polymorphisms and IS susceptibility. A total of 700 IS patients and 700 healthy controls were recruited. The single nucleotide polymorphism (SNP) markers of the MMP-9 gene were genotyped by the MassARRAY analyzer. Multifactor dimensionality reduction (MDR) was applied to generate SNP-SNP interaction. Furthermore, the relationship between genetic variations (allele and genotype) of the MMP-9 gene and IS susceptibility was analyzed by calculating odds ratios (ORs) and 95% confidence intervals (CIs). Our results demonstrated that rs2250889 could significantly increase the susceptibility to IS in the codominant, dominant, overdominant, and log-additive models (p < 0.05). Further stratification analysis showed that compared with the control group, rs2250889 was associated with IS risk in different case groups (age, female, smoking, and non-drinking) (p < 0.05). Based on MDR analysis, rs2250889 was the best model for predicting IS risk (cross-validation consistency: 10/10, OR = 1.56 (1.26-1.94), p < 0.001). Our study preliminarily confirmed that SNP rs2250889 was significantly associated with susceptibility to IS.

Analysis of MMP-2-735C/T (rs2285053) and MMP-9-1562C/T (rs3918242) Polymorphisms in the Risk Assessment of Developing Lung Cancer

Matrix metalloproteinase (MMP)-2 and -9 are gelatinases which are capable of degrading type IV collagen and have been linked to cancer invasion and metastatic development. MMP-2 and MMP-9 gene polymorphisms may affect their biological function, and thus their role in cancer development and progression. We analyzed the association of the polymorphism frequencies of MMP-2-735C/T and MMP-9-1562C/T with MMP-2 and MMP-9 serum concentrations, as well as their potential effects in lung cancer patients. We conducted a retrospective, case-control study consisting of 112 lung cancer patients and 100 healthy individuals from a Caucasian population in Poland. Polymerase chain reaction with restriction fragment length polymorphism (PCR/RFLP) and electrophoresis was used to genotype genomic DNA from whole blood samples. MMP-2 and MMP-9 serum concentrations were then determined using ELISA. For statistical analysis, Statistica version 13 from TIBCO Software Inc. was utilized with a significance level &lt;0.05. Logistic regression analysis revealed that MMP-2-735CC (OR = 5.39; 95% CI = 0.62–47.17; p = 0.238504) and -735CT genotype (OR = 7.22; 95% CI = 0.78–67.14; p = 0.072836), as well as MMP-9-1562CC (OR = 1.45; 95% CI = 0.31–6.70; p = 0.757914) and -1562CT genotype (OR = 1.60; 95% CI = 0.33–7.83; p = 0.548801) were associated with a higher risk of lung cancer. There were statistically significant differences observed in the MMP-2 concentration between individuals with the -735CC genotype and the -735CT genotype (non-smoking control: 204.04 ng/mL vs. 237.00 ng/mL, respectively, p = 0.041479; adenocarcinoma patients: 157.69 ng/mL vs. 126.37 ng/mL, respectively, p = 0.013222), as well as differences in the MMP-9 concentration between individuals with the -1562CC genotype and the -1562CT genotype (smoking control: 385.67 ng/mL vs. 562.80 ng/mL, respectively, p = 0.000936; patients with other lung neoplasms: 821.64 ng/mL vs. 928.88 ng/mL, respectively p = 0.023315). The role of MMP-2-735C/T and MMP-9 -1562C/T polymorphisms in an increased risk of lung cancer cannot be dismissed. Specific genotypes affect MMP-2 and MMP-9 concentrations in both lung cancer patients and healthy controls, which may thereby increase lung cancer risk, disease aggressiveness, and patient survival outcomes.

Importance of MMP-2 and MMP-9 gene polymorphism in the delopment of microvascular complications in type 2 diabetes patients

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Complex studies on gene polymorphisms of MMP2, MMP3, MMP9 matrix metalloproteinases and TIMP1, TIMP2 tissue inhibitors of metalloproteinases in the patients with primary open-angle glaucoma

Abnormal expression of matrix metalloproteinases (MMP) in watery moisture in patients with glaucoma may affect regulation of intraocular pressure (IOP). MMP activity is regulated by tissue metalloproteinase inhibitors (TIMP). The imbalance between tissue metalloproteinase inhibitors and matrix metalloproteinases may contribute to the development of glaucoma. Genetic factors, including polymorphism of matrix metalloproteinase genes and their inhibitors genes, can regulate the level of their expression, thereby affecting susceptibility to disease. Our aim was to perform comprehensive analysis of the MMP2 (rs243865), MMP3 (rs3025058), MMP9 (rs3918242) polymorphisms, and TIMP1 (rs4898), TIMP2 (rs8179090) tissue inhibitor genes polymorphisms in the patients with stage II (advanced) primary open-angle glaucoma.99 patients (52 men and 47 women) with a verified diagnosis of stage II primary open-angle glaucoma were examined. The comparison group consisted of 100 age-matched persons (81 women and 19 men) without ophthalmic disorders. The single-nucleotide polymorphisms in promoter regions of MMP2, TIMP1, TIMP2 genes were analyzed by the TaqMan method, the MMP3 and MMP9 genes, by means of restriction fragment length polymorphism technique. Statistical evaluation was carried out using the specialized package of IBM SPSS Statistics 23 programs. The critical level of significance was assumed to be 0.05.The differences in the distribution of MMP2 rs243865 allelotypes with decreased frequency of TT genotype were found in the patient group and, vice versa, increased heterozygosity rates were revealed among them. In addition, the frequency of TIMP1 rs4898 heterozygous genotype was decreased in this group as compared to control sample. Four MMP/TIMP complex genotypes are positively associated with the development of pathology. Two of them were of bilocus type, i.e., MMP2-1306TC:TIMP2-418GG, and MMP3-11715A6A:TIMP1 372CC whereas two three-locus constellations were revealed, i.e., MMP2-1306TC:MMP9-1562CC:TIMP2- 418GG, and MMP3-11715A6A:MMP9-1562CC:TIMP1 372CC. There are nine MMP/TIMP complexes, the frequency of which in patients with glaucoma was significantly reduced when compared with control group.Polymorphism of regulatory regions of MMP2, MMP3, MMP9 genes and distinct gene variants of their inhibitors (TIMP1, TIMP2 genes) can be considered potential markers of the POAG development associated with an imbalance of MMP/TIMP activities.