MMP-9 Polymorphisms Research Articles

Исследование взаимосвязи полиморфизмов -1612 5A/6A гена MMP3 и 2003G>A гена MMP9 c риском развития ишемической болезни сердца у русских жителей Центральной России

It is known that the proteolysis disorder and changes in metabolism of extracellular matrix proteins cause the process of remodeling heart muscle, which is one of the risk factors for coronary heart disease (CHD). Matrix metalloproteinases (MMPs) are responsible for the process of proteolysis. Single nucleotide substitutions in genes encoding MMPs may influence the functional activity of enzymes. The aim of this study was to investigate the association of polymorphisms -1612 5A/6A (rs3025058) of MMP3 gene and 2003G>A (rs17577) of MMP9 gene with the risk of CHD in population of Central Russia. We studied DNA samples obtained from 946 subjects, including 256 CHD patients and 248 sex- and age-matched healthy individuals. The polymorphisms were genotyped through a real-time PCR using TaqMan allele-discrimination assays. The comparative analysis showed no difference in allele and genotype frequencies of MMP3 and MMP9 polymorphisms between the case and control groups. The study showed that polymorphism -1612 5A/6A of MMP3 gene and polymorphism 2003G>A of MMP9 gene are not associated with coronary heart disease in population of Central Russia.

Role of MMP-2 (-1306 C/T) Polymorphism in Pituitary Adenoma.

Purpose. To determine if the frequency of the genotype of MMP-2 (-1306 C/T) Rs243865 has an influence on the development of pituitary adenoma (PA). Methods. The study enrolled n = 84 patients with PA and a random sample of the population n = 318 (reference group). The genotyping test of MMP-2 (-1306 C/T) was carried out using the real-time polymerase chain reaction method. Results. Analysis of MMP-2 (-1306 C/T) gene polymorphism has not revealed any differences in the genotype (C/C, C/T, and T/T) distribution between the PA patients and the reference group (as follows: 50%, 44%, and 6% versus 59.75%, 33.96%, and 6.29%). MMP-2 (-1306) C/C genotype was rarely observed in noninvasive PA compared to healthy controls: 35.1% versus 59.75%; p = 0.0049, as well C/C genotype being more frequently detected in nonrecurrence PA compared to healthy controls: 46.5% versus 59.75%; p = 0.0468. MMP-2 (-1306) C/T genotype was more frequently present in PA females compared to healthy controls females: 49.1% versus 33.66%; p = 0.041. Conclusion. Patients with noninvasive and nonrecurrence pituitary adenoma were the carriers of the C/C genotype significantly more frequently than their control counterparts and the C/T genotype in females was more frequent.

Polymorphisms of matrix metalloproteinases and their association with metastasis and the efficacy of androgen-deprivation therapy for prostate cancer in Taiwanese men

ObjectiveProstate cancer is a common disease with a multifactorial and complex etiology. Genetic variants influence the level of matrix metalloproteinase (MMP) gene expression and protein function that are involved in susceptibility to and the prognosis of several cancers. Materials and MethodsIn this project, we selected 40 patients with prostate cancer and treated them with androgen-deprivation therapy (ADT). The prostate cancer patients treated with ADT were divided into two groups, those with a time to progression (TTP) < 12 months and those with a TTP > 12 months. The DNA from tumors (biopsy), blood, and oral epithelium cells was collected. The polymorphisms of MMP1 -1607 1G/2G, MMP2 -1306 C/T, MMP3 -1171 5A/6A, MMP8 -799 C/T, and MMP9 -1562 C/T were selected for genotyping. The association of selected polymorphisms and prognosis of prostate cancer and efficacy of ADT were analyzed. ResultsOur preliminary results showed that MMP2 polymorphism-associated metastasis of prostate cancer and MMP 8 polymorphism were associated with the efficacy of ADT (defined by TTP). Furthermore, the association of MMP8 remained significant after adjustment for other factors. ConclusionThe promoter polymorphisms of MMP2 and MMP8 should be genetic markers in the prognosis and TTP of ADT in prostate cancer.

POLYMORPHISMS OF MATRIX METALLOPROTEASES 2 AND 9 GENES IN ASCENDING AORTA ANEURISM PATIENTS

Aim. To study the role of mononucleotide polymorphisms of the matrix metalloproteases genes MMP2 and MMP9 in the development of ascending aorta aneurism (AOA). Material and methods. Totally 287 patients included with AOA and 227 persons of control group. All patients underwent echocardiography and assessment of mononucleotide gene polymorphisms of MMP2 (rs2285053) and MMP9 (rs11697325, rs2274755, rs17577) real-time, by PCR. Results. The association of MMP9 (rs11697325) is confirmed for the formation of AOA. AA genotype was significantly more prevalent among AOA patients (c2 =7,2; p=0,01). AA genotype carriers had higher ascending aorta diameter comparing to other persons with different variants (p=0,02). The relation is shown of the polymorphism ММР2 (rs2285053) and AOA development. Persons with CC genotype were more prevalent in the group of the aorta pathology patients (c2 =7,0; р=0,03). Conclusion. Genetic variants ММР9 and ММР2 can be additional risk factors of ascending aorta aneurism development. Therefore the assessment of different polymorphisms of matrix metalloproteases genes is useful for the risk stratification of the patients with ascending aorta dilation.

Associations of MMP1, MMP2 and MMP3 Genes Polymorphism with Coal Workers’ Pneumoconiosis in Chinese Han Population

Coal workers’ pneumoconiosis (CWP) has been associated with abnormalities in the extracellular matrix remodeling, as well as aberrant matrix metalloproteinases (MMPs) in lung tissues. We investigated the association of three functional polymorphisms in MMP gene promoters (MMP1 rs1799750, MMP2 rs2285053 and MMP3 rs522616) with the risk of CWP. A total of 693 CWP cases and 690 controls were included in a case-control study. Genotype analysis was performed by the TaqMan method. Statistically significant differences were found in distributions of MMP3 rs522616 under a recessive model (p = 0.047) between CWP cases and controls. In the stratification analysis, individuals with MMP3 rs522616 GG genotype decreased the risk of CWP (adjusted OR = 0.72, 95% CI = 0.52–0.99) compared to those with AA/AG genotype obviously, particularly among subgroups of no smokers (adjusted OR = 0.64, 95% CI = 0.41–1.00). Furthermore, serum MMP3 protein levels measured with enzyme-linked immune-sorbent assay in the control group was significantly lower than that in the CWP groups (p = 0.02). Extremely lower MMP3 among subjects with the rs522616 GG or AG genotype compared with the AA genotype carriers (p < 0.05, p < 0.01 respectively) in the normal serum. These findings indicate that the MMP3 rs522616 polymorphism may contribute to the etiology of CWP in the Chinese population and MMP3 might be a potential diagnostic biomarker for CWP, additional independent studies are warranted to validate our findings in different populations as well as in a larger series.

Influence of Matrix metalloproteinase 1 and 3 genetic variations on susceptibility and severity of juvenile idiopathic arthritis

Juvenile idiopathic arthritis (JIA) is a chronic rheumatic disease affecting children aged less than 16 years, characterized by chronic synovitis, cartilage damage, and bony erosions mediated by matrix metalloproteinases (MMPs), mainly MMP-1 and MMP-3. The purpose of this study was to investigate MMP-1 and MMP-3 gene polymorphisms in patients with JIA, the role of genes in susceptibility to JIA, and their associations with JIA activity and prognosis. Case-control study included 100 patients diagnosed with JIA, according to the criteria of the International League of Associations for Rheumatology (ILAR), and 100 healthy children, age and sex matched, as controls. The MMP-1 (-1607 1G/2G) and MMP-3 (-1171 5A/6A) polymorphisms were screened by polymerase chain reaction-restriction fragment length polymorphism. The serum levels of MMP-1 and MMP 3 were measured by enzyme-linked immunosorbent assay. There were significant differences between patients with JIA and control groups regarding the genotype and allele frequencies distributions of both MMP-1 1G/2G and MMP-3 5A/6A polymorphisms. The haplotype 2G-6A, which carries the abnormal alleles, showed higher frequencies in patients with JIA than in controls (OD = 2.8, P = 0.002). The prevalence of MMP-1 2G and 6A allele for MMP-3 polymorphism was found to be significantly associated with persistent oligoarticular, rheumatoid factor (RF)-positive polyarthritis, and systemic JIA groups. There were significantly increased serum levels of MMP-1 and MMP-3 associated with 2G/6A haplotype in the patient group, especially with the polyarticular RF (+ve) group than in other groups and the control group. MMP-1 and MMP-3 haplotypes could be useful genetic markers for JIA susceptibility and severity in the juvenile Egyptian population. Moreover, our data further support the use of serum MMP-3 and MMP-1 as specific markers of disease activity in JIA.

Angiogenesis related genes NOS3, CD14, MMP3 and IL4R are associated to VEGF gene expression and circulating levels in healthy adults.

BackgroundVascular endothelial growth factor (VEGF) plays a key role in angiogenesis. The aim was to assess the genetic connections between the angiogenesis-related NOS3, CD14, MMP3, IL4R, IL4 genes and VEGF expression and plasma levels.MethodsThe associations between VEGF plasma levels with the polymorphisms of NOS3, CD14, MMP3, IL4R, and IL4 were assessed in 403 healthy unrelated adults. The epistatic and environmental interactions were explored, including four VEGF-related polymorphisms previously identified. The VEGF expression in peripheral blood mononuclear cells was quantified (n = 65) for the VEGF121, VEGF145, VEGF165, and VEGF189 isoforms.ResultsThe polymorphism rs1799983 of NOS3 was associated with the sum of all VEGF isoforms mRNA levels (P = 0.032) and VEGF145 (P = 0.033). Rs1800779 of NOS3 interacted with rs3918226 of the same gene and with the rs2569190 of CD14 (P = 0.022, P = 0.042, respectively) for VEGF plasma levels. Other epistatic interactions included the rs1801275 of IL4R with the rs6921438 (VEGF-related variant) and rs3025058 of MMP3 (P = 0.042, P = 0.010 respectively) and the rs2569190 of CD14 with the rs3025058 of MMP3 (P = 0.0119). We also identified an interaction of rs1800779 with obesity, high-density lipoprotein cholesterol and triglycerides (P = 0.018, P = 0.005, P = 0.043, respectively) as well as the interaction of rs6921438 with hypertension (P = 0.028).ConclusionsOur findings indicated that genetic variants of NOS3, CD14, MMP3 and IL4R are implicated in the determination of VEGF expression and plasma levels. Thus, they support the hypothesis that in physiological conditions there are complex biological relationships between pathways (such as angiogenesis and inflammation), which are involved in the development of chronic diseases.Electronic supplementary materialThe online version of this article (doi:10.1186/s12881-015-0234-6) contains supplementary material, which is available to authorized users.

Genetic polymorphisms of matrix metalloproteinases and protein levels in chronic obstructive pulmonary disease in a Mexican population.

To evaluate association of single nucleotide polymorphisms (SNPs) in the MMP1, MMP2, MMP9 and MMP12 genes and serum MMP-2 and MMP-9 levels in smoking chronic obstructive pulmonary disease (COPD) patients. Genotyping using real-time PCR in 330 smokers with COPD (COPD), 658 smokers without COPD (SNC) and 150 nonsmokers (NCNS), the analysis of samples used was χ(2) test. Using ELISA, the proteins were evaluated. Multiple comparisons were made by ANOVA. rs243864 (OR: 7.44; 95% CI: 3.62-15.26) and rs11646643 (OR: 1.58; 95% CI: 1.07-2.34) of the MMP-2 gene and rs3918253 (OR: 1.72; 95% CI: 1.08-2.71) of the MMP-9 gene, were associated with the risk of COPD. Serum MMP-2 level in the COPD group was lower compared with SNC (p < 0.05). Serum MMP-9 level was elevated in the COPD group compared with SNC (p < 0.05). Polymorphisms in MMP2 and MMP9 but not in MMP1 and MMP12 are associated with the risk of COPD in the Mexican mestizo population.

Analysis of the association between polymorphisms in MMP2, MMP3, MMP9, MMP20, TIMP1, and TIMP2 genes with white spot lesions and early childhood caries.

Matrix metalloproteinases and their inhibitors might be involved in enamel formation. This study aimed to evaluate the association between polymorphisms in MMP2, MMP3, MMP9, MMP20, TIMP1, and TIMP2 with white spot lesions (WSL) and early childhood caries (ECC). A cross-sectional study was performed on 786 children aged from 2 to 6 years in Brazil. After clinical evaluation, they were classified into groups with disease (the presence of WSL and/or ECC) and without disease (the absence of WSL or ECC). Genotyping of the selected polymorphisms was carried out with TaqMan real-time PCR, using genomic DNA extracted from buccal cells. Allele and genotype frequencies were compared between groups. Chi-square test, odds ratio (OR), and logistic regression were used (P ≤ 0.05). The dmft score was 1.3 (SD: 2.4), and 41.34% of the children have at least one caries lesion. In MMP9, the GG genotype was more frequent in the group without disease (P = 0.006). In a recessive model, WSL was associated with the marker rs1711437 in MMP20 (P = 0.019; OR = 1.20, 95% CI 1.02-1.42). The marker rs1784418 in MMP20 showed an association between the allele G distribution for the WSL group (P = 0.020; OR = 0.73, 95% CI 0.55-0.96). MMP9 and MMP20 are involved in WSL and ECC development.

Growth Rate of Small Abdominal Aortic Aneurysms and Genetic Polymorphisms of Matrix MetalloProteases-1, -3, and -9

Genetic variants of matrix metalloproteases (MMPs)-1, -3, and 9, together with clinical variables, might predict the growth rate (GR) of abdominal aortic aneurysm (AAA). Genotyping of MMP-1 (-1,607 G+/G-), MMP-3 (- 1,171 6A/5A), and MMP-9 microsatellite (13-26 cytosine-adenosine repeats around -90) from peripheral blood was performed in 137 AAA patients with two AAA diameter measurements (at least 3 months to 1 year apart). When the same technique (either ultrasound or computed tomography) was used for the two measurements, yearly GR was estimated and compared with MMP genotype and clinical features by linear and binary logistic regression. Collectively, 36 patients provided 94 observations, with a median GR of 3 mm/year (interquartile range, 0-5.8); GRs in carriers of MMP-1 polymorphism G-/G-, G-/G+, and G+/G+ genotype were 0.3, 3.5, and 4.7mm/year, respectively (p = 0.008). In linear logistic regression, the main determinant of GR was growth arrest (GA, i.e., GR = 0, occurring in 32 observations, 34%). In turn, GA occurred mainly in G-/G- MMP-1 genotype (odds ratio, 3.9; 95% confidence interval, 1.6-9.7; p = 0.002), while variables accounting for GR > 0 were MMP-1 G + /G+ genotype, intake of any antihypertensive drug, and MMP-3 6A/6A genotype. Carriers of none, one, or two/three of these conditions accounted for a GR of 3, 4, and 9 mm/year, respectively (p = 0.001). MMP-1 (-1,607 G+/-) variant is associated to differential GR in AAA: homozygous G deletion variant shows higher GA prevalence and lower GR, while carriers of G + /G+ MMP-1 genotype, together with intake of antihypertensive drugs, and 6A/6A in MMP-3 present cumulative GR increase.

Genetic Polymorphism of MMP2 Gene and Susceptibility to Prostate Cancer

The polymorphic genetic variants of matrix metalloproteinase (MMPs) can play critical roles in development and progression of cancer. The purpose of this study was to investigate if any association exists between MMP2 -1306/T and risk of prostate cancer (PCa). This case-control study comprised a total number of 241 subjects, including 102 patients with PCa and 139 controls with benign prostatic hyperplasia (BPH). MMP2 genotypes were detected by RFLP. There is no significant difference between different genotypes of MMP2 polymorphism and risk of developing PCa (p = 0.08). Although these genotypes increased the risk of developing PCa 79% (CT vs. CC) and 54% (TT vs. CC), none had a significant effect (p = 0.09 and p = 1 respectively). There were no significant differences in genotype frequencies between patients with low and high degrees of PCa (p = 0.4). Therefore, this polymorphism cannot be considered as a protective factor for PCa metastasis. It seems that MMP2 polymorphism has no protective effect on the grading of the tumor (p = 0.8). Our results indicated that MMP2 polymorphism had no role in the vascular invasion of PCa. We found no association between MMP2 polymorphism and cancer risk, overall or by grade, stage or age of diagnosis. Finally, there was no association between the different genotypes and PSA plasma levels among cases or controls. Further evaluations with larger samples from our population may illuminate the effects of polymorphisms on PCa risk and thus help early diagnosis, follow-up and prognostic determinations for PCa patients.

MMP1, 2, 3, 7, and 9 gene polymorphisms and urinary cancer risk: a meta-analysis.

The matrix metalloproteinases (MMPs) are a family of highly conserved, metal-dependent proteolytic enzymes that play an important role in tumor invasion and metastasis. Many studies have been carried out on the association between polymorphisms in the MMP1, MMP2, MMP3, MMP7, and MMP9 genes and urinary cancer risk. However, the data from these published studies are conflicting and have low statistical power. In this study, we performed a meta-analysis of 12 different publications from the PubMed and WanFang databases, published up to May 2015, to better assess the purported associations. Odds ratios (OR) and 95% confidence intervals (CI) were determined to reveal association strengths. Some significant associations were found. For the MMP1 -1607 1G/2G polymorphism, a negative association was identified for the 2G allele in bladder cancer (2G2G+2G1G vs. 1G1G: OR = 0.57, 95% CI = 0.36-0.93, pheterogeneity = 0.001) and renal cell carcinoma (2G1G vs. 1G1G: OR = 0.57, 95% CI = 0.39-0.82, pheterogeneity = 0.567). For the MMP2 -1306 C/T polymorphism, there was a negative association with the T allele for bladder cancer in the Asian population (TT+TC vs. CC: OR = 0.41, 95% CI = 0.18-0.94, pheterogeneity = 0.195). For the MMP7 -181 A/G polymorphism, a decreased bladder cancer risk was found (G-allele vs. A-allele: OR = 0.81, 95% CI = 0.66-0.98, pheterogeneity =0.325). In summary, our study showed evidence that genetic polymorphisms in MMP1 for all populations, but only in the Asian population for MMP2 and MMP7, may protect against bladder cancer risk. Future studies with larger sample sizes are warranted to further evaluate these associations in more detail.

Association of matrix metalloproteinase family gene polymorphisms with lung cancer risk: logistic regression and generalized odds of published data.

Many studies have reported the association between the matrix metalloproteinase (MMP) polymorphisms and lung cancer susceptibility, but the results were inconclusive. We conducted a meta-analysis, using a comprehensive strategy based on the logistic regression and a model-free approach, to derive a more precise estimation of the relationship between MMP1, MMP2, MMP9 and MMP13 polymorphisms with lung cancer risk. A total of 22 case-control studies including 8202 cases and 7578 controls were included in this meta-analysis. For MMP1-1607 1G/2G, increased lung cancer risk was found among Asians in additive model(OR = 1.34, 95%CI:1.18-1.53) and with model-free approach(ORG = 1.41, 95%CI:1.21-1.65). For MMP2-1306 C/T and -735 C/T, based on the model-free approach, a significantly reduced risk was found in Asians(MMP2-1306 C/T:ORG = 0.49,95%CI:0.42-0.57; MMP2-735 C/T: ORG = 0.71, 95%CI:0.61-0.84). For MMP9-1562 C/T, a significantly increased risk was found among Asians(OR = 2.73, 95%CI:1.74-4.27) with model-free approach. For MMP13-77A/G, there was no association between this polymorphism and lung cancer risk in the recessive model(OR = 1.02, 95%CI:0.83-1.26) and with the model-free approach(ORG = 0.95, 95%CI:0.76-1.17). Therefore, this meta-analysis suggests that the MMP1-1607 1G/2G, MMP2-1306 C/T, MMP2-735 C/T, MMP9 -1562 C/T polymorphisms were risk factors for lung cancer among Asians, while MMP13 -77A/G polymorphism was not associated with lung cancer risk.

The VEGFR2, COX-2 and MMP-2 polymorphisms are associated with clinical outcome of patients with inoperable non-small cell lung cancer.

Certain common inherited variations in genes involved in tumor angiogenesis, progression and metastasis may contribute to cancer therapy outcome and prognosis by altering the gene expression and protein activity. In this report, we examined the effect of functional polymorphisms in MMP-1, MMP-2, MMP-3, VEGF, VEGFR2, FGFR4 and COX-2 genes on overall (OS) and progression-free survival (PFS) of 350 Caucasian patients with inoperable non-small cell lung cancer (NSCLC). The results of multivariate analysis indicated that VEGFR2 -906C and COX-2 -1195G alleles were strongly associated with poor OS and PFS (p = 0.002 and 0.015, respectively, for OS; p = 0.009 and 0.015, respectively, for PFS), while MMP-2 -1306 T allele carriers had significantly reduced PFS (p = 0.010). Moreover, an increased risk of death and progression was significantly associated with the number of adverse alleles for VEGFR2/COX-2 (p = 0.0005 for OS and 0.0006 for PFS in >1 adverse allele carriers) and VEGFR2/COX-2/MMP-2 combinations (p = 0.0003 for OS and 0.0001 for PFS in patients with >2 adverse alleles). Finally, VEGFR2 TC/CC, COX-2 AG/GG and MMP-2 CT/TT genotypes as well as "at risk" allele combinations were identified as independent predictors of unfavorable OS and PFS in the group. In conclusion, the data suggest that selected VEGFR2, COX-2 and MMP-2 polymorphisms may be potential prognostic markers in unresectable NSCLC treated with radiotherapy with or without chemotherapy, although further validation studies are warranted to confirm our observations.

Matrix metalloproteinase-9 polymorphism 1562 C > T (rs3918242) associated with protection against placental malaria.

Phagocytosis of malaria pigment (hemozoin) induces increased activity of matrix metalloproteinase (MMP)-9, an endopeptidase involved in cytokine regulation. In this study, we examined whether a common functional MMP-9 promoter polymorphism (rs3918242) affects Plasmodium falciparum infection in pregnancy. Eighteen percent of Ghanaian primiparae carried the minor T allele. It was associated with reduced odds of placental hemozoin and of placental as well as peripheral blood parasitemia. The results indicate that a common MMP-9 polymorphism protects against placental malaria indicating that this endopeptidase is involved in susceptibility to P. falciparum.

Association of MMP-9 Haplotypes and TIMP-1 Polymorphism with Spontaneous Deep Intracerebral Hemorrhage in the Taiwan Population.

BackgroundSpontaneous deep intracerebral hemorrhage (SDICH) is a devastating stroke subtype. The causes of SDICH are heterogeneous. Matrix metalloproteinase-9 (MMP-9, Gelantinase B) has been shown to relate to stroke and the development of aneurysm and may increase risks of intracerebral hemorrhage. MMP activities are modulated by their endogenous inhibitors, tissue inhibitors of metalloproteinases (TIMPs). We analyzed the genetic variants of MMP-9 and TIMP-1 and SDICH susceptibility.MethodsAssociations were tested by logistic regression or general linear models with adjusting for multiple covariables. Multiplicative terms between genes were applied to detect the interaction effects on SDICH. Permutation testing of 1,000 replicates was performed for empirical estimates.ResultsIn the group of ≥65 years old (y/o), we found associations of SDICH with rs3787268 (Odds ratio [OR] = 0.48, 95% confidence interval [CI] 0.27 to 0.86, P = 0.01) and haplotype1 (Hap1) (OR = 0.48, 95% CI 0.26 to 0.86, P = 0.014). For TIMP1 gene, rs4898 was associated with SDICH in the elder male group (OR = 0.35, 95% CI 0.15 to 0.81, P = 0.015). In contrast, in the younger male group, there were associations of SDICH with rs2250889 (OR = 0.48, 95% CI 0.27 to 0.84, P = 0.01) and Hap3 (OR = 0.61, 95% CI 0.38 to 0.97, P = 0.04). We found significant genetic interaction between TIMP-1 and MMP-9 in SDICH susceptibility among younger male subjects (P = 0.004). In subjects carrying rs4898 minor allele, carriers with Hap3 had lower SDICH risk than non-carriers (OR = 0.19, 95% CI 0.07 to 0.51, P = 0.001). In addition, this study showed that when young males were exposed to alcohol, Hap3 was a protective factor of SDICH (OR = 0.06, 95% CI 0.01 to 0.27, P = 0.0002). In contrast, when they were exposed to smoke, Hap2 carriers had increased risk of SDICH (OR = 2.45, 95% CI 1.05 to 5.73, P = 0.04).ConclusionsThis study showed modest to moderate effects of MMP-9 and TIMP-1 polymorphisms on SDICH risks with significant age differences. MMP-9 may interact with alcohol to play a role in the SDICH risk in young men.

Association between matrix metalloproteinase-2 and matrix metalloproteinase-9 polymorphisms and endometriosis: A systematic review and meta-analysis.

Matrix metalloproteinase-2 (MMP-2)-735C/T and MMP-9-1562C/T polymorphisms have been indicated in the predisposition to endometriosis. However, due to the small sample sizes of previous studies, the results remain inconclusive. The present meta-analysis was conducted to detect the association between the two genetic polymorphisms and the risk of endometriosis by pooling all the available data. Electronic databases, including PubMed, Embase, Web of Science and CNKI, were searched comprehensively for studies examining a link between MMP-2 and MMP-9 polymorphisms and endometriosis. The strength of the association was assessed based on the pooled odds ratio with a 95% confidence interval, which was calculated using either the fixed- or random-effect model. Following the inclusion criteria, 6 case-control studies were included. The total number of participants was 2,486 (558 cases and 797 controls concerning the MMP-9-1562C/T polymorphism, and 525 cases and 606 controls concerning the MMP-2-735C/T polymorphism). No significant association was identified between the MMP-2-735C/T or MMP-9-1562C/T polymorphism and endometriosis. In further stratified analysis, no significant association was identified between the MMP-9-1562C/T polymorphism and endometriosis. The present meta-analysis revealed no association between the MMP-2-735C/T and MMP-9-1562C/T polymorphisms and the risk of developing endometriosis. Considering the limitations of the meta-analysis, well-designed studies with larger sample sizes are required.

Polymorphisms of MMP-1 and MMP-3 and susceptibility to rheumatoid arthritis. A meta-analysis.

To determine the correlation between rheumatoid arthritis (RA) and polymorphisms of the matrix metalloproteinase (MMP) genes MMP-1 and MMP-3. The 16071G/2G and 11715A/6A polymorphisms of MMP genes MMP-1 and MMP-3 have been discovered to be functional, and may be conducive to RA. In order to determine whether MMP-1 and MMP-3 gene polymorphisms correlate with RA development, we performed a meta-analysis to further validate the function of these polymorphisms in RA. We searched PubMed, ISI Web of Knowledge, MEDLINE, Embase, Google Scholar Chinese Biomedical Literature Database, and Wanfang Data to identify all published case-control studies on the MMP-1-16071G/2G and MMP-3-11715A/6A polymorphisms and RA risk. Odds ratios (OR) and 95 % confidence intervals (CI) were used to estimate the association between these polymorphisms and RA risk. After being assessed, five articles fulfilled the inclusion criteria. To assess associations, the pooled OR with 95 %CIs was calculated. Neither the MMP-1-16071G/2G nor the MMP-3-11715A/6A polymorphism was statistically associated with RA in any of the five models, nor in the subgroup analysis models of MMP-3-11715A/6A in Caucasian and Asian patients. Our study suggests that MMP-1 and MMP-3 polymorphisms have no significant association with the risk of RA.

Matrix Metalloproteinases 2 and 9 Polymorphism in Patients With Myeloproliferative Diseases: A STROBE-Compliant Observational Study.

Chronic myeloproliferative disorders such as polycythemia vera (PV), essential thrombocytosis (ET), and idiopathic myelofibrosis arise from clonal proliferation of neoplastic stem cells in the bone marrow. Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases that have potential to degrade all types of extracellular matrix (ECM) and also play a role in remodeling of the ECM. It is known that MMPs play a role in bone marrow remodeling.The primary goal of our study is to explore the relationship between chronic myeloproliferative diseases and some of MMP gene polymorphisms. The demonstration of a relationship will help to understand whether these polymorphisms may be a potential early diagnosis marker of the diseases.Patients were selected from outpatient clinics of Turgut Ozal University Hospital, Ankara, Turkey, between December 2010 and May 2011. Twenty-eight patients that previously diagnosed and followed-up with PV, 17 with secondary polycythemia (SP), and 12 with ET were enrolled in the study, along with a control group of 22 healthy people.DNA was isolated from peripheral blood. Using polymerase chain reaction–restriction fragment length polymorphism method, MMP2 and MMP9 gene polymorphisms were analyzed with agarose gel electrophoresis. There was a statistically significant difference between the study groups and the control group in terms of Gln279Arg polymorphisms rates of MMP9. The highest MMP9 Gln279Arg polymorphism rate was observed in the ET group. But nobody from the control group had polymorphic MMP9. There was no statistically significant difference between the groups in terms of MMP2-735 C > T polymorphism rates.In conclusion, MMP9 gene Gln279Arg polymorphism was associated with ET, SP, and PV diseases. Hence, we believe that these gene polymorphisms may play a role in the mechanism of bone marrow fibrosis and may be a factor that increases the risk of thrombosis. Illumination of the molecular basis of the relationship between MMP-thrombosis and MMP-fibrosis provides a better understanding of the pathophysiology of PV and ET diseases and will allow new approaches to diagnosis and treatment.

Polymorphisms in IL-10 and INF-γ genes are associated with early atherosclerosis in coronary but not in carotid arteries: A study of 122 autopsy cases of young adults

Atherosclerosis is a complex disease, involving both genetic and environmental factors. However, the influence of genetic variations on its early development remains unclear. This study examined the association of 12 different polymorphisms with atherosclerosis severity in anterior descending coronary (DA, n=103) and carotid arteries (CA, n=66) of autopsied young adults (<30years old). Histological sections (H-E) were classified according to the American Heart Association. Polymorphisms in ACE, TNF-α (−308G/A and −238G/A), IFN-γ (+874 A/T), MMP-9 (−1562 C/T), IL-10 (−1082 A/G and −819 C/T), NOS3 (894G/T), ApoA1 (rs964184), ApoE (E2E3E4 isoforms), and TGF-β (codons 25 and 10) genes were genotyped by gel electrophoresis or automatic DNA sequencing. Firearm projectile or car accident was the main cause of death, and no information about classical risk factors was available. Histological analysis showed high prevalence of type III atherosclerotic lesions in both DA (69%) and CA (39%) arteries, while severe type IV and V lesions were observed in 14% (DA) and 33% (CA). Allele frequencies and genotype distributions were determined. Among the polymorphisms studied, IFN-γ and IL-10 (−1082 A/G) were related to atherosclerosis severity in DA artery. No association between genotypes and lesion severity was found in CA. In conclusion, we observed that the high prevalence of early atherosclerosis in young adults is associated with IFN-γ (p<0.001) and IL-10 (p=0.013) genotypes. This association is blood vessel dependent. Our findings suggest that the vascular system presents site specialization, and specific genetic variations may provide future biomarkers for early disease identification.