Metalloproteinase Gene Polymorphisms Research Articles

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.

Association of matrix metalloproteinase gene polymorphisms with different biological subtypes of breast cancer

Aim. To investigate the associations of matrix metalloproteinase (MMP) MMP3 (rs679620), MMP8 (rs1940475), and MMP9 (rs17576 and rs3787268) gene polymorphisms with different biological subtypes of breast cancer (BC).&#x0D; Materials and methods. The study sample consisted of 285 patients with BC of various biological subtypes (luminal A and B [n=153], triple negative [n=108], and HER2 positive [HER2+, n=24]) and 746 females in the control group. Genotyping of four polymorphic sites of MMP3 (rs679620), MMP8 (rs1940475), and MMP9 (rs17576 and rs3787268) genes was performed in the study groups.&#x0D; Results. The role of MMP gene polymorphisms in the BC development of various biological subtypes differs. The c.836 AG MMP9 polymorphism (rs17576, the odds ratio is 0.670.71 for the G allele) has a protective effect on the development of luminal A- and B-subtypes of BC; susceptibility to triple-negative BC is associated with the polymorphic site c.1331-163 GA MMP9 (rs3787268, OR 4.51 for genotype AA), and two polymorphisms of the MMP3 (c.133 TC, rs679620, OR 0.460.49 for T allele) and MMP8 (c.259 TC, rs1940475, OR 0.370.48 for T allele) genes are associated with HER2+ BC development. According to the in silico data, the above polymorphisms have pronounced functional effects in organs and tissues that are pathogenetically significant for the disease, including the target organ, the breast.&#x0D; Conclusion. The c.836 AG MMP9 (rs17576) polymorphism is associated with luminal A- and B-subtype of BC; c.1331-163 GA MMP9 (rs3787268) is associated with triple negative BC, and c.133 TC MMP3 (rs679620) and c.259 TC MMP8 (rs1940475) are involved in HER2+ BC development.

Matrix Metalloproteinase Gene Polymorphisms Are Associated with Breast Cancer in the Caucasian Women of Russia.

We conducted this study to explore the association between matrix metalloproteinase (MMP) gene polymorphisms and breast cancer (BC) risk in the Caucasian women of Russia. In total, 358 affected (BC) and 746 unaffected (cancer-free) women were included in this case-control retrospective study. From BC-related genes in previous studies, ten single nucleotide polymorphisms (SNPs) in five MMP genes (MMP1, 2, 3, 8, 9) were genotyped. The BC risk was calculated by logistic regression (to evaluate the SNPs’ independent effects) and model-based multifactor dimensionality reduction (MB-MDR) (to identify SNP–SNP interactions) methods. The allelic variants’ distribution of c.836 A > G (rs17576) and c. 1721 C > G (rs2250889) MMP9 was significantly different between BC and cancer-free women: for G minor alleles, these SNPs manifested disorder protective effects (OR 0.82 and OR 0.67–0.71, respectively, pperm ≤ 0.035). Eleven haplotypes of six SNPs MMP9 were involved in BC risk (nine haplotypes) and protective (two haplotypes) effects. All 10 SNPs of the MMP genes examined were associated with BC within the 13 SNP–SNP interaction simulated models, with a pivotal role of the two-locus (rs17577 × rs3918242) MMP9 epistatic interaction (defined as 1.81% BC entropy within more than 60% of the genetic models). Under in silico bioinformatics, BC susceptibility MMP polymorphic loci are located in functionally active genome regions and impact genes expression and splicing “regulators” in the mammary gland. The biological pathways of BC MMP candidate genes are mainly realized due to metalloendopeptidase activity and extracellular matrix organization (structure, disassembly, metabolic process, etc.). In conclusion, our data show that MMP gene polymorphisms are related to BC susceptibility in the Caucasian women of Russia.

The Modifying Effect of Obesity on the Association of Matrix Metalloproteinase Gene Polymorphisms with Breast Cancer Risk.

Objective: We investigated the possible modifying effect of obesity on the association of matrix metalloproteinase (MMP) gene polymorphisms with breast cancer (BC) risk. Methods: A total of 1104 women divided into two groups according to their body mass index (BMI): BMI ≥ 30 (119 BC, and 190 control) and BMI < 30 (239 BC, and 556 control) were genotyped for specially selected (according to their association with BC in the previous study) 10 single-nucleotide polymorphisms (SNP) of MMP1, 2, 3, 8, and 9 genes. Logistic regression association analysis was performed in each studied group of women (with/without obesity). Functional annotation of BC-correlated MMP polymorphic variants was analyzed by in silico bioinformatics. Results: We observed significant differences in the involvement of MMP SNPs in BC in obese and non-obese women. Polymorphic loci MMP9 (c.836 A > G (rs17576) and c. 1721 C > G (rs2250889)) were BC-protective factors in obese women (OR 0.71, allelic model, and OR 0.55, additive model, respectively). Genotypes TT MMP2 (c.-1306 C > T,rs243865) and AA MMP9 (c. 1331-163 G > A,rs3787268) determined BC susceptibility in non-obese women (OR 0.31, and OR 2.36, respectively). We found in silico substantial multidirectional influences on gene expression in adipose tissue BC-related polymorphic loci: BC risk allele A-rs3787268 in non-obese women is associated with low expression NEURL2, PLTP, RP3-337O18.9, SPATA25, and ZSWIM1, whereas BC risk allele A-rs17576 in obese women is associated with high expression in the same genes in visceral and/or subcutaneous adipose. Conclusions: our study indicated that obesity has a significant modifying effect on the association of MMP genes with BC risk in postmenopausal women.

Relationship between tissue inhibitors of metalloproteinases (TIMPS) gene polymorphisms and risk of spontaneous intracerebral hemorrhage: A systematic review and meta-analysis

Relationship between tissue inhibitors of metalloproteinases (TIMPS) gene polymorphisms and risk of spontaneous intracerebral hemorrhage: A systematic review and meta-analysis

Matrix metalloproteinase gene polymorphisms in chronic periodontitis: a case–control study in the Indian population

Chronic periodontitis (CP) is the common form of inflammatory oral disease. Matrix metalloproteinases (MMPs) play a pivotal role in the progression of CP by degrading gingival tissue and its remodelling. Here, we conducted a case-control study to investigate a possible association of single-nucleotide polymorphism of MMP genes and their interaction with CP in the Indian population. A total of 357 DNA samples of venous blood was isolated, of which 157 were identified as CP patients and 200 were healthy individuals. Genotyping of six MMP genes (MMP1, MMP3, MMP7, MMP8, MMP12 and MMP13) was done using polymerase chain reaction following Sanger's method of sequencing. Statistical analyses were performed by SPSS v16.0, R package (SNPassoc). Gene-gene interactions were evaluated by MDR 3.0.2. The frequency of 6A allele of MMP3 -11715A-6A gene polymorphisms (36%) and G allele of MMP8 +17G-C gene polymorphisms (34%) were higher in the CP population compared with the healthy population (19% and 24%, respectively). A significant association of T allele of MMP8 -799C-T gene promoter polymorphism was found with CP (OR = 2.95, 95%CI = 2.16 - 4.04, P < 0.0001). Genotypic frequency of MMP12 -82A-G polymorphism is associated with CP risk while its allelic distribution is not (OR = 1.32, 95%CI = 0.93 - 1.88, P = 0.129). Gene-gene interactions show the best cross validation consistency model, i.e. MMP1 -519A-G X MMP7 -181A-G X MMP8 -799C-T polymorphismswith a value of 9/10. This gene-gene interaction shows that the significant association of MMP8 -799C-T polymorphism with CP increased susceptibility. Allelic distribution of MMP8+17G-C and MMP3-11715A-6A polymorphisms revealed their protective role towards decreased risk of CP. MMP1 -519A-G and MMP7 -181A-G polymorphisms show combinatorial synergistic effect on CP risk.

The Relationship between Matrix Metalloproteinase Gene Polymorphisms and Tumor Type, Tumor Size, and Metastasis in Women with Breast Cancer in Central Iran

Background: Matrix metalloproteinases-2 and -9 play important roles in the development of breast cancer by hydrolyzing the extracellular matrix. Since −1306C/T and −1562C/T polymorphisms are located at the promoter regions of the matrix metalloproteinase- 2 and -9 genes, respectively, C to T substitution may affect promoter activity and impact the rate of extracellular matrix degradation and cancerous cell proliferation. Therefore, we aimed to determine the genotype and allele frequencies of these polymorphisms in Iranian healthy women and women with breast cancer. We have also examined the correlation of genotypes with clinicopathological parameters such as tumor type, tumor size, and metastasis to lymph nodes. Methods: This case-control study enrolled 200 women with breast cancer and 200 age-matched healthy women. DNA was extracted, and we determined the genotype and allele frequencies of −1306C/T matrix metalloproteinase-2 and −1562C/T matrix metalloproteinase-9 polymorphisms by the polymerase chain reaction-restriction fragment length polymorphism method. Additionally, tumor size (20 mm), tumor type (ductal/non-ductal), and metastasis (yes/no) were determined. Results: Genotype and allele frequencies of the −1306C/T matrix metalloproteinase- 2 polymorphism showed no significant association with the occurrence of breast cancer. Genotype and allele distribution differed in the −1562C/T matrix metalloproteinase- 9 polymorphism and indicated a 4.83-fold increase in the risk of breast cancer for T allele carriers. There was no likelihood of any interaction found between the two polymorphisms and susceptibility to breast cancer. In addition, the −1562C/T matrix metalloproteinase-9 T allele showed an association with metastasis to lymph nodes but we observed no association between the −1306C/T matrix metalloproteinase- 2 polymorphism and clinicopathological features. Conclusion: The ‒1562C/T matrix metalloproteinase-9 polymorphism is involved in the pathogenesis of breast cancer in Iranian women. The T allele may increase the risk of disease.

Matrix metalloproteinase and tissue inhibitors of metalloproteinases gene polymorphisms in disorders that influence fertility and pregnancy complications: A systematic review and meta-analysis

Matrix metalloproteinase (MMP) and tissue inhibitors of metalloproteinase (TIMP) gene polymorphisms have been extensively evaluated as predisposing factors to human reproductive disorders. However, the evidence available is inconsistent. Therefore, we performed a systematic review and meta-analysis to provide the first comprehensive synopsis of case-control studies that investigated the association of MMP and TIMP gene polymorphisms with disorders that influence fertility and pregnancy complications. Literature search was performed using PubMed and Scopus databases. We included 42 case-control studies in the systematic review for the following disorders: adenomyosis, endometriosis, hypertensive disorders of pregnancy, preterm birth and recurrent spontaneous abortion. Although a large number of MMP and TIMP gene polymorphisms were tested, no exclusive and unambiguous risk factors were identified for any of the disorders. The majority of statistically significant associations were confirmed in just one study. Additionally, we performed two meta-analyses for MMP9 rs3918242 polymorphism in endometriosis/adenomyosis and preeclampsia but found no association with either disorder. Considering the modest associations and conflicting results between individual case-control studies, new data is needed for further research of this subject.

Genetic Association between Matrix Metalloproteinases Gene Polymorphisms and Risk of Prostate Cancer: A Meta-Analysis.

Background and Objective: Studies suggests that matrix metalloproteinase (MMP)-2-1306 C/T and MMP-1-1607 1G/2G polymorphisms affect the risk of prostate cancer. However, the conclusions remain controversial and no pooled evidence of this topic has been published. Therefore, we aimed to perform a meta-analysis to shed some light on the controversial conclusion pertaining to the associations of MMP-2-1306 C/T and MMP-1-1607 1G/2G polymorphisms with prostate cancer susceptibility.Methods: A thorough literature search was performed up to August, 2016 with the PubMed, EMBASE, CBM, CNKI, and Wanfang databases. Odds ratios (ORs) and corresponding 95% confidence intervals (95% CIs) were calculated to address the correlations between these polymorphisms and risk of prostate cancer.Results: The meta-analysis included six studies (1,921 patients and 1,988 controls) on MMP-2-1306 C/T polymorphism and three studies on MMP-1-1607 1G/2G polymorphism (438 patients and 394 controls), respectively. The overall results of meta-analysis showed that an elevated risk of the disease was implicated in MMP-2-1306 C/T polymorphism under two genetic models (CT vs. CC: OR = 1.78, 95% CI = 1.33–2.38; TT+CT vs. CC: OR = 1.62, 95% CI = 1.24–2.12) and no significant association was observed between MMP-1-1607 1G/2G polymorphism and the risk of prostate cancer. The subgroup analysis results of MMP-2-1306 C/T polymorphism were similar to the overall results. However, decreased risk of prostate cancer was observed in the Caucasians for MMP-1-1607 1G/2G polymorphism.Conclusions: Current meta-analysis indicates that MMP-2-1306 C/T polymorphism is associated with elevated risk of prostate cancer, but MMP-1-1607 1G/2G polymorphism may inhibit the occurrence of prostate cancer in Caucasians. Further studies are warranted to verify the conclusions.

Matrix Metalloproteinase Gene Polymorphisms in Periodontitis in Taiwanese Population

Matrix Metalloproteinase Gene Polymorphisms in Periodontitis in Taiwanese Population

Association of R279Q and C1562T polymorphisms of matrix metalloproteinase 9 gene and increased risk for myocardial infarction in patients with premature coronary artery disease.

A number of matrix metalloproteinase (MMP) gene polymorphisms has been identified which may be probably related to premature myocardial infarction (MI). We assessed the relationship between the two polymorphisms of the MMP9 gene including R279Q and C1562T and occurrence of premature MI. The study has two phases including a case-control study as the first phase and cohort study as the second phase. Initially, 1000 patients with premature coronary artery disease were classified into MI and non-MI groups. Genotyping of the polymorphism was conducted by PCRRFLP and high-resolution melting techniques. Given the two conditions of patients residing in Tehran and faced with their first episode of MI, 640 of 1000 study samples previously followed up with a median follow-up time of 45.74months were assessed in a retrospective cohort phase regarding long-term major adverse cardiac events (MACE). The prevalence of wild, heterozygous, and mutant genotypes of R279Q polymorphism in MI group was 14.5%, 57.3%, and 28.2% and in non-MI group was 36.9%, 38.4%, and 24.7%, respectively, with a considerable difference (P<.001). There was a significant difference in the prevalence of wild, heterozygous, and mutant genotypes of C1562T polymorphisms in MI group (12.4%, 41.2%, and 46.4%, respectively) and in non-MI group (46.8%, 38.6%, and 14.7%, respectively; P<.001). No difference was found in total MACE-free survival rate between genotypes of R279Q and C1562T polymorphisms. C1562T and R279Q polymorphisms are associated with the susceptibility to premature MI, but cannot predict long-term cardiac events in these patients.

Associations between matrix metalloproteinase gene polymorphisms and glaucoma susceptibility: a meta-analysis

BackgroundMatrix metalloproteinases (MMPs) polymorphisms have been implicated in the pathogenesis of glaucoma risk. However, the results were controversial. We performed a meta-analysis to evaluate the precise associations between MMPs polymorphisms and glaucoma risk.MethodsRelated studies were reviewed by searching electronic databases within four databases. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to assess the association between the most common polymorphisms of MMPs and glaucoma risk. Heterogeneity, publication bias and sensitivity analysis were conducted to guarantee the statistical power.ResultsOverall, 11 selected articles involving 2,388 cases and 2,319 controls were included in this meta-analysis. Significant associations were only found between MMP-9 rs17576 G > A polymorphism (GA vs. GG: OR = 0.80, 95%CI = 0.67-0.97, P = 0.02, I2 = 0%), MMP-9 rs3918249 C > T polymorphism (TT vs. CC + CT: OR = 0.71, 95%CI = 0.51-0.98, P = 0.04, I2 = 0%) and glaucoma risk in the general population. Subgroup analysis also suggested that MMP-9 rs17576 G > A was related to glaucoma in the Caucasian population (GA vs. GG: OR = 0.67, 95%CI = 0.45-1.00, P = 0.05; GA + AA vs. GG: OR = 0.66, 95%CI = 0.45-0.97, P = 0.03, I2 = 0%).ConclusionsOur meta-analysis demonstrates that MMP-9 rs17576 G > A polymorphism might be a protective factor against the development of glaucoma in Caucasian population.

Matrix Metalloproteinase Gene Polymorphisms and New-Onset Diabetes After Kidney Transplantation in Korean Renal Transplant Subjects

BackgroundNew-onset diabetes after transplantation (NODAT) is a serious metabolic complication that may follow renal transplantation. Matrix metalloproteinases (MMPs) contribute to insulin insufficiency and beta-cell dysfunction in a rat model. The MMP-2 concentrations were lower in patients with type 2 diabetes mellitus, and the plasma MMPs levels were related to diabetes. Similar to the pathogenesis of type 2 diabetes mellitus, insulin resistance and insulin secretion dysfunction occur in patients with the development of NODAT. Therefore, we examined the association between NODAT and 11 single-nucleotide polymorphisms (SNPs) located within the 3 genes of MMPs that might be related to NODAT. MethodsA total of 309 renal transplant recipients without a history of diabetes were included in this study. DNA was extracted from the blood samples of recipients, and we analyzed the association between the development of NODAT and a panel of 11 SNPs within 3 MMP genes (MMP-1, MMP-2, and MMP-3). ResultsIn terms of allele frequencies, rs243849*C (MMP-2) was significantly higher in patients with NODAT. Two of the 11 (18.1%) SNPs were significantly associated with NODAT development after adjusting for age, sex, and tacrolimus usage: MMP-2 (rs1132896) and MMP-2 (rs243849). In the multiple logistic regression analysis, these 2 SNPs were significantly associated with the development of NODAT in the codominant and recessive or codominant and dominant models. ConclusionsMMP-2 gene rs1132896 and rs243849 polymorphisms may serve as genetic markers for the development of NODAT. The exact molecular mechanisms still must be clarified.

Matrix metalloproteinase gene polymorphisms and periodontitis susceptibility: a meta-analysis involving 6,162 individuals.

We aimed to systematically investigate the potential association of matrix metalloproteinase (MMP)-9, -3, -2, and -8 gene polymorphisms with susceptibility to periodontitis using meta-analysis. A literature search in PubMed, Embase, and Web of Sciencewas conducted to obtain relevant publications. Finally a total of 16 articles with 24 case-control studies (nine on MMP-9-1562 C/T, seven on MMP-3-1171 A5/A6, four on MMP-2-753C/T, and four on MMP-8-799 C/T) were considered in this meta-analysis. The results based on 2,724 periodontitis patients and 3,438 controls showed that MMP-9-1562C/T, MMP-3-1171 A5/A6, and MMP-8-799C/T polymorphisms were associated with periodontitis susceptibility. No significant association was found between MMP-2-753 C/T and periodontitis susceptibility. Subgroup analyses suggested that the MMP-9-1562 C/T polymorphism reduced chronic periodontitis susceptibility and MMP-3-1171 A5/A6polymorphism increased chronic periodontitis susceptibility. In summary, current evidence demonstrated that MMP-9-753 C/Tpolymorphism reduced the risk of periodontitis, MMP-3-1171 5A/6A and MMP-8-799 C/Tpolymorphisms increased the risk of periodontitis, and MMP-2-753 C/T was not associated with risk of periodontitis.

Associations between matrix metalloproteinase gene polymorphisms and the development of cerebral infarction

The aim of this study was to investigate the association between MMP3 rs3025058 and MMP9 rs3918242 polymorphisms and the development of ischemic stroke in a Chinese population. Between May 2013 and January 2015, 335 patients with ischemic stroke and 335 health control subjects were enrolled in this study. The MMP3 rs3025058 and MMP9 rs3918242 polymorphisms were analyzed using polymerase chain reaction coupled with restriction fragment length polymorphism. By multivariate logistic regression analysis, the CC genotype of MMP9 rs3918242 was shown to be associated with a significantly increased risk of ischemic stroke when compared with the TT genotype [OR (95%CI) = 5.47 (2.64-12.38)]. The TC+CC genotype of MMP9 rs3918242 was furthermore found to be associated with an elevated risk of ischemic stroke in higher BMI individuals [OR (95%CI) = 1.81 (1.03-3.22)]. The findings of this study suggest that the MMP9 rs3918242 polymorphism is associated with an elevated risk of ischemic stroke and that this gene polymorphism interacts with BMI in the risk of ischemic stroke.

Matrix metalloproteinase gene polymorphisms and susceptibility to systemic sclerosis.

The major pathological hallmark of the systemic sclerosis (SSc) is skin and internal organ fibrosis, which results from normal tissue architecture alterations and extracellular matrix (ECM) protein deposition. ECM components are degraded by matrix metalloproteinases (MMP). Promoter region polymorphisms in MMP genes may influence gene expression, resulting in an imbalance between ECM protein production and degradation. Here, we analyzed MMP1 -1607 1G/2G (rs1799750), MMP3 -1171 5A/6A (rs3025058), and MMP9 -1562 C/T (rs3918242) polymorphisms in relation to susceptibility to SSc and its clinical features. The patient group included 98 individuals with longstanding or recently diagnosed disease, meeting the American College of Rheumatology or LeRoy and Medsger criteria for SSc; the control group included 100 healthy blood donors. All participants were of European descent. Genotyping was performed by polymerase chain reaction followed by restriction digestion. Genotype and allele frequencies of MMP polymorphisms were similar between the two groups. In secondary analyses, significantly higher frequency of 1G/2G genotype from MMP1 polymorphism was observed for patients testing positive for antinuclear autoantibodies (P = 0.007), while 1G/1G genotype was associated with interstitial lung disease development (P = 0.018). The 6A/6A genotype from MMP3 polymorphism was absent in patients with calcinosis (P = 0.011), while the MMP3 5A/5A genotype correlated with the presence of anti-topoisomerase I antibodies (P = 0.009) and reduced diffusing capacity for carbon monoxide (P = 0.024). These results suggest that MMP polymorphisms are not associated with SSc susceptibility, although MMP1 and MMP3 variants are associated with specific SSc clinical and laboratory features.

Association Study of Matrix Metalloproteinases Gene Polymorphisms with Susceptibility to Rheumatoid Arthritis: A Meta-Analysis

Objective: Association of matrix metalloproteinases (MMPs) gene polymorphisms with rheumatoid arthritis is controversial. We conduct a meta-analysis to clarify this dispute.Methods: We systematically searched the electronic PUBMED, EMBASE and CNKI databases for research articles about MMPs (MMP-1, MMP-2, MMP-3, MMP-9) gene polymorphisms and rheumatoid arthritis (RA) up to January 2015. According to the heterogeneity, fixed-effects or random-effects models were used to calculate crude odds ratios (ORs) and 95% confidence intervals (95% CIs).Results: A total of 11 articles involving 2143 cases and 2049 controls were included in this meta-analysis. Overall, no significant associations were observed between MMP-1-1607 1G/2G polymorphism and RA. Stratification by ethnicity, no significant associations were observed in Caucasian populations. Similarly, no significant associations were observed between MMP-3-1171 5A/6A, MMP-9-1562 C/T polymorphisms and RA in overall and Caucasian populations, respectively. However, a weak association was found between MMP-2-1306 C/T polymorphism and RA (C vs. T, OR = 0.813, 95%CI = 0.694–0.953, p = 0.010) in overall populations.Conclusions: The present meta-analysis suggests that MMP-1-1607 1G/2G, MMP-3-1171 5A/6A, MMP-9-1562 C/T polymorphisms are not associated with the susceptibility of RA, but MMP-2 -1306 C/T is weakly associated with susceptibility to RA. Further studies with more sample size are needed for definitive conclusions.

Association of tissue inhibitor of metalloproteinase gene polymorphisms and unexplained recurrent spontaneous abortions in Han Chinese couples

ObjectiveTo investigate the association of tissue inhibitor of metalloproteinase (TIMP) gene polymorphisms with unexplained recurrent spontaneous abortions (URSA) in a well-defined group of Han Chinese couples. Study designThis is a case-control association study. Genomic DNA was extracted from peripheral blood samples from 84 couples with histories of three or more pregnancy losses and 69 age-matched healthy couples with at least one live birth and no histories of pregnancy loss. Polymerase chain reactions (PCRs) and sequencing with the fluorescent dye dideoxy-termination method were used to detect the rs4898 in TIMP-1, rs2277698 in TIMP-2, rs2234921 and rs5749511 in TIMP-3 and rs17035945 in TIMP-4 genotypes and allele frequencies. ResultsNeither the allele frequencies nor any of the genetic model of the five TIMP gene SNPs (i.e., TIMP-1-rs4898, TIMP-2-rs2277698, TIMP-3-rs5749511 and rs2234921, and TIMP-4-rs7035945) were significantly differences between the URSA couples and the control group. ConclusionsNo evidence was found for any associations between the TIMP-1,-2,-3, or -4 genes SNPs with URSA in this Han Chinese Han.

Lack of association between matrix metalloproteinase-9 gene-1562C/T polymorphism and preeclampsia: a meta-analysis

Studies investigating the association between matrix metalloproteinases (MMPs) gene polymorphisms and preeclampsia (PE) reported contradictory or non-conclusive results. We performed a meta-analysis of five studies that examined the relationship between PE and the MMP9-1562C>T polymorphism. The PubMed, Embase, and Google Scholar databases were searched to access the relevant genetic association studies up to September 2013. The meta-analysis revealed that there was no evidence for significant association between MMP9-1562C>T polymorphism and risk of PE. Large, multiethnic confirmatory, and well-designed studies are needed to further explore the relation between preeclampsia and polymorphisms of the MMPs gene.

QRS Widening Rates and Genetic Polymorphisms of Matrix Metalloproteinases in a Cohort of Patients With Chronic Heart Failure

BackgroundQRS duration is considered to be an indicator of adverse outcome in patients with heart failure (HF), and genetic polymorphisms may be involved in this conductivity impairment. We studied the prognostic impact of the QRS widening rate (QRS-WR) on patients with HF and the influence of the matrix metalloproteinases gene polymorphisms on the QRS-WR. MethodsThis prospective cohort study included 184 patients with left ventricular (LV) systolic dysfunction (LV ejection fraction [LVEF] < 45%). The QRS-WR was calculated as the difference between 2 electrocardiogram assessments (in ms) divided by the time elapsed between each evaluation (months). The MMP-1 -1607 1G/2G, MMP-2 -790G/T and -1575G/A, MMP-3 -1171 5A/6A, MMP-9 -1562 C/T and R279Q, and MMP-12 -82A/G polymorphisms were genotyped using polymerase chain reaction–restriction fragment length polymorphism. ResultsPatients were predominantly white (68%) men (67%) in New York Heart Association functional classes I and II (77%). Patients with HF with a QRS-WR ≥ 0.5 ms/month had more HF-related deaths and more combined clinical events than those with a QRS-WR < 0.5 ms/month (P = 0.03 and P = 0.01, respectively). After adjusting for other covariates, the QRS-WR remained an independent predictor of combined clinical events (hazard ratio, 1.6; 95% confidence interval, 1.1-2.5; P = 0.02). The MMP-1 2G2G genotype was associated with nearly a 2-fold increase in QRS-WR (P = 0.03). Conversely, patients with the MMP-3 5A5A genotype and a nonischemic cause of HF were protected against QRS enlargement (P = 0.03). ConclusionsQRS-WR retains prognostic value in patients with chronic HF receiving guideline-based pharmacologic treatment. MMP gene polymorphisms can influence the rate of QRS enlargement over time.