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Matrix metalloproteinases (MMPs) family gene polymorphisms and the risk of multiple sclerosis: systematic review and meta-analysis.

ABSTRACT: BACKGROUND:Several studies have reported the association between polymorphisms in Matrix metalloproteinases (MMPs) gene family and risk of Multiple sclerosis (MS). However, the results have been inconsistent and inconclusive. To resolve this issue, here we performed a systematic review and meta-analysis of the MMP-91562 C/T (rs3918242), MMP-3 (-?1612 5A/6A), and MMP-2 (-?1306 C/T) polymorphisms and susceptibility to MS. METHODS:We conducted a comprehensive systematic search in the major electronic database, including Scopus and PubMed to look up for relevant studies published before December 2019 that surveyed the association between the MMP-91562 C/T (rs3918242), MMP-3 (-?1612 5A/6A), and MMP-2 (-?1306 C/T) polymorphisms and susceptibility to MS. The level of association between the polymorphisms and susceptibility to MS in the polled analysis was determined by calculating the odds ratio (OR) and the corresponding 95% confidence interval (CI). RESULTS:We found 15 studies containing 2430 MS subjects and 2304 controls. A statistically significant association was observed in the all five comparisons of the MMP-91562 C/T polymorphism and MS risk as follows: dominant model (OR?=?1.62, 95% CI?=?1.03-2.53, P?=?0.03), recessive model (OR?=?2.69, 95% CI?=?1.68-4.29, P?

SUBMITTER: Mohammadhosayni M

PROVIDER: S-EPMC7257507 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Matrix metalloproteinases (MMPs) family gene polymorphisms and the risk of multiple sclerosis: systematic review and meta-analysis.

Mohammadhosayni Mina M Khosrojerdi Arezou A Lorian Keivan K Aslani Saeed S Imani Danyal D Razi Bahman B Babaie Farhad F Torkamandi Shahram S

BMC neurology 20200529 1

<h4>Background</h4>Several studies have reported the association between polymorphisms in Matrix metalloproteinases (MMPs) gene family and risk of Multiple sclerosis (MS). However, the results have been inconsistent and inconclusive. To resolve this issue, here we performed a systematic review and meta-analysis of the MMP-91562 C/T (rs3918242), MMP-3 (- 1612 5A/6A), and MMP-2 (- 1306 C/T) polymorphisms and susceptibility to MS.<h4>Methods</h4>We conducted a comprehensive systematic search in the ...[more]

PMID: 32471473

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Project description:Published data on the relationship between matrix metalloproteinases (MMPs) polymorphisms and ovarian cancer risk have implicated inconclusive results. To evaluate the role of MMPs polymorphisms in ovarian cancer risk, a meta-analysis and systematic review were performed.MMPs polymorphisms which could be quantitatively synthesized were involved in meta-analysis. Five comparison models (homozygote model, heterozygote model, dominant model, recessive model, additive model) were carried out, a subgroup analysis was performed to clarify heterogeneity source. The remaining polymorphisms which could not be quantitatively synthesized were involved in systematic review.10 articles with 20 studies were included in this paper. Among those studies, 8 studies involving MMP1 rs1799750 and MMP3 rs34093618 could be meta-analyzed and 12 studies involving 12 polymorphisms could not. Meta-analysis showed that no associations were found between MMP1 rs1799750 (homozygote model: OR = 0.93, 95%CI = 0.70-1.23, POR = 0.60; heterozygote model: OR = 1.09, 95%CI = 0.78-1.54, POR = 0.61; dominant model: OR = 1.02, 95%CI = 0.83-1.25, POR = 0.84; recessive model: OR = 0.95, 95%CI = 0.75-1.21, POR = 0.67; additive model: OR = 1.00, 95%CI = 0.85-1.17, POR = 0.99), MMP3 rs34093618 (homozygote model: OR = 1.25, 95%CI = 0.70-2.24, POR = 0.46; heterozygote model: OR = 1.08, 95%CI = 0.51-2.31, POR = 0.84; dominant model: OR = 0.97, 95%CI = 0.68-1.38, POR = 0.85; recessive model: OR = 1.12, 95%CI = 0.69-1.80, POR = 0.65; additive model: OR = 1.01, 95%CI = 0.79-1.31, POR = 0.91) and ovarian cancer. Furthermore, similar results were detected in subgroup analysis. The systematic review on 12 polymorphisms suggested that MMP2 C-735T, MMP7 A-181G, MMP8 rs11225395, MMP9 rs6094237, MMP12 rs2276109, MMP20 rs2292730, MMP20 rs12278250, MMP20 rs9787933 might have a potential effect on ovarian cancer risk.In summary, polymorphisms of MMPs might not be associated with ovarian cancer risk. However, it is necessary to conduct more larger-scale, multicenter, and high-quality studies in the future.

Project description:BACKGROUND:Chronic alcohol consumption has been shown in human and animal studies to result in collagen accumulation, myocardial fibrosis, and heart failure. Cardiac fibroblasts produce collagen and regulate extracellular matrix (ECM) homeostasis through the synthesis and activity of matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs), with the balance of MMPs/TIMPs determining the rate of collagen turnover. Dynamic changes of MMP and TIMP expression were reported in alcohol-induced hepatic fibrosis; however, the effect of alcohol on MMP/TIMP balance in the heart and cardiac fibroblasts is unknown. We hypothesized that alcohol exposure alters cardiac fibroblast MMP and TIMP expression to promote collagen accumulation in the heart. METHODS:Cardiac fibroblasts isolated from adult rats were cultured in the presence of alcohol (12.5 to 200 mM) for 48 hours. MMP, TIMP, and collagen type I and III expression were assayed by Western blot analysis. Hydroxyproline (HPro) was used as a marker of collagen production. The in vivo cardiac effects of ethanol (EtOH) were determined using rats exposed to EtOH vapor for 2 weeks, resulting in blood alcohol levels of 150 to 200 mg/dl. Cardiac collagen volume fraction (CVF), as well as MMP, TIMP, and collagen expression, was assessed. RESULTS:EtOH-exposed rats exhibited up-regulation of TIMP-1, TIMP-3 and TIMP-4 in the heart, with no significant increases in MMPs. Cardiac fibroblasts exhibited transformation to a profibrotic phenotype following exposure to alcohol. These changes were reflected by increased ?-smooth muscle actin and collagen I and III expression, as well as increased collagen secretion. In vivo EtOH exposure also produced fibrosis, indicated by increased CVF and expression of collagens. CONCLUSIONS:Alcohol exposure modulates cardiac fibroblast MMP/TIMP expression favoring a profile associated with collagen accumulation. Our data suggest that this disrupted MMP/TIMP profile may contribute to the development of myocardial fibrosis and cardiac dysfunction resulting from chronic alcohol abuse.

Project description:BackgroundMatrix metalloproteinases (MMPs) are involved in remodeling of the extracellular matrix (ECM) during pregnancy and parturition. Aberrant ECM degradation by MMPs or an imbalance between MMPs and their tissue inhibitors (TIMPs) have been implicated in the pathogenesis of preterm labor, however few studies have investigated MMPs or TIMPs in maternal serum. Therefore, the purpose of this study was to determine serum concentrations of MMP-3, MMP-9 and all four TIMPs as well as MMP:TIMP ratios during term and preterm labor.MethodsA case control study with 166 singleton pregnancies, divided into four groups: (1) women with preterm birth, delivering before 34 weeks (PTB); (2) gestational age (GA) matched controls, not in preterm labor; (3) women at term in labor and (4) at term not in labor. MMP and TIMP concentrations were measured using Luminex technology.ResultsMMP-9 and TIMP-4 concentrations were higher in women with PTB vs. GA matched controls (resp. p = 0.01 and p<0.001). An increase in MMP-9:TIMP-1 and MMP-9:TIMP-2 ratio was observed in women with PTB compared to GA matched controls (resp. p = 0.02 and p<0.001) as well as compared to women at term in labor (resp. p = 0.006 and p<0.001). Multiple regression results with groups recoded as three key covariates showed significantly higher MMP-9 concentrations, higher MMP-9:TIMP-1 and MMP-9:TIMP-2 ratios and lower TIMP-1 and -2 concentrations for preterm labor. Significantly higher MMP-9 and TIMP-4 concentrations and MMP-9:TIMP-2 ratios were observed for labor.ConclusionsSerum MMP-9:TIMP-1 and MMP-9:TIMP-2 balances are tilting in favor of gelatinolysis during preterm labor. TIMP-1 and -2 concentrations were lower in preterm gestation, irrespective of labor, while TIMP-4 concentrations were raised in labor. These observations suggest that aberrant serum expression of MMP:TIMP ratios and TIMPs reflect pregnancy and labor status, providing a far less invasive method to determine enzymes essential in ECM remodeling during pregnancy and parturition.

Project description:BackgroundMultiple sclerosis (MS) and stroke are two common causes of death and disability worldwide. The relationship between these two diseases remains unclear. Effective early preventative measures and treatments are available to reduce the morbidity and mortality of acute stroke. The objectives of our systematic review are to estimate the risk of stroke in patients with MS and to collate related studies to draw preliminary conclusions that may improve clinical practice.MethodRelevant studies were systematically searched in MEDLINE, Embase, the Chinese Biomedical Literature Database (CBM), the China National Knowledge Infrastructure and the VIP database of Chinese periodicals from January 1983 to May 2017, with no restrictions on language. Patients included in this review were adults who suffered from MS. Review Manager 5.3 software program was used to pool data and calculate the risk ratio (RR) and its 95% confidence interval (CI). We also performed heterogeneity and sensitivity analyses and evaluated bias in the meta-analysis.ResultsNine studies including more than 380,000 participants that met our inclusion criteria were incorporated into the meta-analysis. During different follow-up periods, patients with MS had an increased risk of any type of stroke [RR = 3.48, 95% CI (1.59, 7.64), P = 0.002 for 1 year; RR = 2.45, 95% CI (1.90, 3.16), P < 0.00001 for 10-13 years]. The total prevalence of stroke (any type) in patients with MS exceeded expectations compared to different groups [Comparing with general veteran: RR = 2, 95% CI (1.19, 3.38), P = 0.009. Comparing with general population: RR = 2.93, 95% CI (1.13, 7.62), P = 0.03]. Furthermore, ischemic stroke was particularly more common in the MS population than in people without MS [RR = 6.09, 95% CI (3.44, 10.77), P < 0.00001].ConclusionCompared with the general population, people with MS have an increased risk of developing any type of stroke and ischemic stroke in particular. Consistent results were obtained from patients of different sexes and age groups. Preventative measures and treatments should be administered at earlier time points to improve patient outcomes.

Dataset Information

Matrix metalloproteinases (MMPs) family gene polymorphisms and the risk of multiple sclerosis: systematic review and meta-analysis.

Publications

Matrix metalloproteinases (MMPs) family gene polymorphisms and the risk of multiple sclerosis: systematic review and meta-analysis.

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