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Continuous variables with normal distribution were compared between groups by the Student t-test and those with skewed distribution were compared with the Mann-Whitney U test. The Kolmogorov-Smirnov test was used to verify the normality of quantitative variables.

Categorical variables, including the genotype and allele frequencies, were compared by the Pearson chi-square or the likelihood-ratio chi-square test, as appropriate. Allele frequencies were determined by gene counting and departures from Hardy-Weinberg equilibrium were verified with the chi-square test. We also used PHASE to compare the distribution of different MMP-2 haplotypes between groups of subjects, computing P-values by a permutation test with 1, random replicates.

To evaluate whether MMP-2 gene polymorphisms are related to HF prognosis, Kaplan-Meier survival curves were constructed considering the period between the date of the first visit at the outpatient clinic and the last registry of follow-up or death. Survival curves obtained for the different genotypes and haplotypes were compared by the log-rank test.

Whenever appropriate, models were adjusted for the demographic and clinical variables that were associated with HF prognosis in the univariate analyses.

Statistical analyses were done using SPSS version Baseline characteristics of HF patients are summarized in Table 1. Caucasian-Brazilians had predominantly ischemic etiology, whereas African-Brazilians had more often hypertensive HF Table 1. Genotype frequencies did not deviate significantly from those predicted by the Hardy-Weinberg equation for all polymorphisms in Caucasian-Brazilians and African-Brazilian HF patients. However, we found more homozygotes for the minor allele than the expected for the 3 polymorphisms among African-Brazilian blood donors.

As shown in Table 2 , the allele frequencies were similar in HF patients and blood donors for all polymorphisms in both ethnic groups. However, among African-Brazilians, genotype frequencies were different between HF patients and blood donors, as none of the HF patients was homozygote for the minor alleles. As shown in Table 3 , haplotype frequencies in HF patients were very similar to those observed in blood donors, in both ethnic groups.

During a median follow-up of 5. Among the patients who died, 68 In relation to all-cause and HF-related mortality, we observed that heterozygous patients had the worst survival rates.

Among African-Brazilian patients, survival curves were quite similar in heterozygotes and homozygotes for the major alleles for all polymorphisms Fig 2. In fact, the rate of HF-related death was lower in TT homozygous patients than in heterozygous patients In relation to African-Brazilians, the frequencies of the homozygous genotypes for the minor alleles of the 3 MMP-2 polymorphisms were nearly 2. This suggests that the carriership of the AA, AA, or GG genotypes could be associated with a reduced risk of HF, thus partly in line with the Chinese study [ 22 ].

In the report by Hua et al. However, these associations were lost after adjusting for clinical covariates. These findings partially agree with those reported by Hua et al. Differences in the prevalence of cardiovascular diseases, natural history of HF, and response to therapy have been attributed, among other factors, to interethnic differences in the frequency of common genetic variants [ 40 , 41 ]. Our findings reinforce this assumption, as we also detected several differences in the genotype and allele frequencies of the 3 MMP-2 polymorphisms comparing Caucasian-Brazilian, African-Brazilian and north Han Chinese controls [ 22 ].

The absence of such an association in African-Brazilians due to lack of statistical power is unlikely, as the survival curves were virtually identical in both heterozygotes and homozygotes for the major alleles. Population differences could explain, at least in part, the contrasting findings observed by us and Hua et al.

In line with this, Kim et al. Brazilian population is known to be highly admixed. However, a study using ancestry informative markers showed that people living in the four most populous Brazilian regions have a predominant European ancestry In Rio Grande do Sul State, where our study was done, people defined as White have a predominant European ancestry Despite its limitation, our ethnic classification reflects the findings reported by Cardena et al. Even though we did not use the ancestry informative markers to define ethnicity, stratifying the analyses by the two most prevalent self-declared ethnic groups in our region should have minimized the potential bias of population stratification.

In this context, heterogeneity of HF etiology is another factor that could be thought as a confounder. In the Chinese studies [ 22 , 24 ], patients had reduced LVEF caused by myocardial infarction in the past or idiopathic dilated cardiomyopathy, whereas our cohort was composed of patients who had ischemic, idiopathic, hypertensive, valvular, chagasic, or alcoholic cardiomyopathy. MMP-2 gene polymorphisms have been investigated in association studies based on their putative effects on gene expression at the transcriptional level.

It included epithelial cells , macrophages RAW Although considered by Price et al. The opposite was observed in A10 cell line, that expresses estrogen receptor-beta but not alpha , with the G transfectants expressing 1. Later, Harendza et al. Additional experiments showed that these differences in allelic expression were related to the binding of the estrogen receptor-alpha to this region.

This is in line with what was observed in the study of Price et al. In A10 cells, in contrast, the T allele showed a lower promoter activity compared with the G allele 0.

These data suggest that polymorphisms in the promoter of MMP-2 gene might influence gene expression in a cell-type specific manner, as already discussed by Price et al.

In their functional study, Price et al. Moreover, Harendza et al. Taken together, these data indicate that the effect of individual polymorphisms on MMP-2 gene expression is modest and might influence the susceptibility and prognosis of HF in an additive manner.

Considering there are interpopulation differences in the allele frequencies of MMP-2 variants, their functional effect may vary according to genetic background, thus leading to differential findings across populations. Given the evidence from observational studies in humans demonstrating that MMP-2 levels are positively correlated with LV remodeling early after myocardial infarction and worse HF prognosis [ 11 — 17 ], we would expect that alleles that are less transcriptionally active were associated with decreased risk of developing HF and death.

On the other hand, estradiol and its receptors exert protective effects on cardiomyocytes, whereby they regulate cardiac metabolism, attenuate cardiomyocyte apoptosis, promote cardiac regeneration, modulate physiological and pathological LV hypertrophy, and calibrate electrical and contractile function of the heart [ 45 ]. In this scenario, allelic variants of the MMP-2 gene with reduced transcriptional activity would promote a diminished response to estradiol, thus reducing its beneficial effects on cardiac function, especially in HF patients who already have structural and functional LV impairment.

This could explain the seemingly paradoxical findings from previous studies that showed that patients carrying genotypes associated with higher expression of MMPs had a more favourable HF prognosis [ 25 ], and reduced LV mass index and LV end-diastolic diameter [ 46 ].

Our study has some methodological limitations. First, the retrospective study design with regard to susceptibility of HF does not allow us to assess whether the MMP-2 polymorphisms influence on LV remodeling and which alleles would be involved in this process. Given the potential effect of gender on the development and progression of HF, we repeated the analyses stratifying by gender and ethnic group. In brief, the frequency distribution of MMP-2 genotypes and haplotypes in HF patients and blood donors is in line with those observed for the joint analysis of males and females.

Separate survival analysis for males and females showed similar profiles to those reported for males and females analyzed together. However, statistically significant differences between genotypes or haplotypes were detected only in Caucasian-Brazilian males, maybe because the number of males was almost twice than that of females S2 Fig.

However, given the lack of a replication cohort, the loss of association in the multivariate analyses, and the limitations considered above, our findings should be interpreted with caution and need to be addressed in further larger studies.

Data curation: KGS. Project administration: KGS. Supervision: KGS. Validation: ERP. Visualization: ERP. Browse Subject Areas? Click through the PLOS taxonomy to find articles in your field. Abstract Circulating levels of matrix metalloproteinase-2 MMP-2 predict mortality and hospital admission in heart failure HF patients.

Introduction Heart failure HF is a clinical syndrome of insufficient cardiac output resulting from myocardial injury that remains a leading cause of morbidity and mortality worldwide [ 1 , 2 ]. Statistical Analysis Continuous variables with normal distribution were compared between groups by the Student t-test and those with skewed distribution were compared with the Mann-Whitney U test. Download: PPT. Table 1. Table 2. Table 3.

Fig 1. Fig 2. Fig 3. Supporting Information. S1 Fig. S2 Fig. S1 File. Clinical Data of Heart Failure Patients. S1 Table. S2 Table. S3 Table. S4 Table. S5 Table. S6 Table.

References 1. Epidemiology and risk profile of heart failure. Nat Rev Cardiol. Braunwald E. Heart failure. Dorn GW 2nd. The genomic architecture of sporadic heart failure. Circ Res. Membrane-associated matrix proteolysis and heart failure. Ventricular-arterial coupling, remodeling, and prognosis in chronic heart failure. J Am Coll Cardiol. Myocardial matrix metalloproteinase inside out and upside down.

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During that time, she worked as a financial lead, managing the financial aspect of Epicor ERP implementations. Zarina has a strong understanding of the interactions between Epicor ERP production and financial modules, while her expertise focused on the Financial Management modules, including Multi-Site and Multi-Company environments.

Zarina is fluent in English and Spanish. She uses a combination of both to ensure smooth implementations. She has managed several large-scale multi-company, multi-site, and multi-languages projects.

In addition, her skills include XSOL, a process modeling software. She has worked with clients in the mining, automotive, electronics, medical, food distribution, and industrial parts industries.

Gezeta is a certified senior consultant in the production, distribution, tools, and financial modules. Before his Epicor consulting career with Tomerlin-ERP, Steve was a Senior Development Lead for Cricket Communications leading numerous business initiative implementations and system integrations for mycricket.

He was responsible for estimates, design, team management, implementation, defect management, and critical production issue support triage and resolution.

Dwayne is a dedicated business problem solver. Dwayne has built custom solutions for a vast array of industries including aerospace, automotive and apparel. Dwayne has been recognized for his willingness to tackle the toughest and most complex issues.

He is highly skilled in Epicor development tools to build automated solutions. In his free time, Dwayne enjoys cooking, traveling, and all things basketball. These implementations included an array of industries where he provided configuration, data transfer, management, end-user training, program customization, forms, and more.

Brent enjoys fixing things and has an extensive mechanical passion. He has restored several older vehicles and equipment to their former glory as a hobby. Notice: JavaScript is required for this content. About Us. Implementing Epicor Kinetic requires both business experience and in-depth knowledge of the Epicor Kinetic ERP software, which is the basis of our success.

Our Consulting Team. He has worked with customers throughout the entire evolution of the Epicor system, from the early version of Vista and Vantage through the deployment of Epicor ERP.

Jeremiah has written thousands of custom utilities for customers of all industries. This allows the custom forms sales order acknowledgment, packing slips, invoice, etc to be modified for a professional look, complete with your logos and color schemes. These tools help to facilitate data entry and retrieval by your end-users. Don is a certified senior consultant in the production, distribution, and financial modules. Kerry is a certified senior consultant in the production and distribution modules.

Mike is certified in Epicor tools. Their knowledge of our Epicor ERP system combined with their knowledge of finance and cost accounting has made them a tremendous resource for our company.

We could never have implemented our Epicor ERP system without them. Epicor Software Corp, one of the oldest software-related concerns in the world, is not only helping companies grow their business and increase their efficiency through enterprise resource planning ERP software and systems but also assisting them in their Industry 4. Andy Coussins, senior vice-president and head of international, says the software giant — which started in as a manufacturing software company — has put major investment dollars into Industry 4.

But Epicor is not just looking at these technologies in general. It is honing in on solutions for industries such as manufacturing, retail, food and beverage and distribution. ERP, for the uninitiated, refers to a suite of integrated applications that a business can use to collect, store, manage and interpret data from its business activities. It provides an integrated and continuously updated view of core business processes and helps a company to keep track of its resources such as cash, raw materials and production capacity, as well as the status of its business commitments such as purchase orders and payroll.

The Hong Kong office would take orders from overseas customers and then, it would need to issue a purchase order to the factory in China. Once the products were manufactured, they would need to ship the finished goods to Hong Kong.

Tang points out that it was an unnecessarily lengthy process with a lot of redundancy. So basically, when they receive an order, the job order for the factory is generated automatically and the goods are manufactured.

Once the goods are manufactured, they are shipped out and the customer is automatically sent an invoice. How much did Ka Shui spend on the software? I do not have the key performance indicators so I do not know how much it saved. But I do know that when Ka Shui started using Epicor, it had two small factories. Now, it has moved to a factory that is about four times bigger than the previous two combined. It has gone from being a small manufacturer to the third largest die-casting company in Hong Kong and southern China.

He adds that Epicor has also helped Ka Shui in its digital transformation journey. After a few years of using the Epicor system, it did an internal review of where it was at, and it has just received its Industry 4. Hong Kong has recognised that getting Industry 4. It has to be done in stages. He points out that Industry 4. But with our open technology, we can integrate our solutions with robotics and PLM.

Tang says the Hong Kong Productivity Council, a semi-government body that provides consultancy to manufacturers in Hong Kong, has actually set up an Industry 4. This is the way to educate local manufacturers so they understand what the journey to Industry 4. They cannot get there overnight.

Tang admits that its solutions may not be for small companies that do not have the budget.

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Our Values Our values are the glue that connects us globally - defining our beliefs, informing our decisions, and driving our actions. Proactive Proud Partners We imagine, create, and deliver excellence.

We love what we do and we do what we say. We are truly a team and win as one. Posted Sep Internships — Kick start your career Epicor! Monterrey, MEX,Mexico. I'm interested Share this job:. Tomerlin has in-depth business experience and knowledge; he excels at managing people; he understands and can identify the significant issues that must be addressed and resolved to be successful.

He makes sure everyone has a sense of ownership in the implementation process. Epicor Software Corporation has relied on us to serve some of its most valued customers. We have worked with Epicor ERP customers since Those customers have been in every state in the lower 48 states, in northern Mexico and eastern Canada.

Phone: Email: monte tomerlin-erp. Jon is experienced with both core and supplemental installs for all versions of Epicor ERP, and he is certified for all Epicor ERP and related installations. He has delivered certification training in the APICS and helped many companies improve their lead time, capacity utilization, and profitability by adopting these principles.

Don holds a Ph. Joanne is also fluent in French and English and is a certified senior consultant in the production, distribution, and financial modules. He has worked extensively with Vista, Vantage, and E9 products. Ropelato, with his client, American Nutrition, was an active participant in the Beta testing of Epicor 9.

He has worked primarily with clients in the aerospace, electronics, food, foundry, and industrial parts industries during his software consulting career. Kerry has primarily been a hands-on consultant with Epicor ERP products, managing implementation, and training projects. He has worked for small startups and Fortune companies, including Microsoft, Amazon, and Amdocs.

Daniel is certified in Epicor installations and tools. Mike takes pride in designing and building fault-tolerant, scalable solutions. The United States Postal Service, Department of Defense, IRS, Twitter, plus many banks, manufacturers including Ferrari , telecoms, insurers, and hospitals have solutions he developed, touching the lives of billions across the planet each day.

During that time, she worked as a financial lead, managing the financial aspect of Epicor ERP implementations. Zarina has a strong understanding of the interactions between Epicor ERP production and financial modules, while her expertise focused on the Financial Management modules, including Multi-Site and Multi-Company environments.

Zarina is fluent in English and Spanish. She uses a combination of both to ensure smooth implementations. She has managed several large-scale multi-company, multi-site, and multi-languages projects.

In addition, her skills include XSOL, a process modeling software. She has worked with clients in the mining, automotive, electronics, medical, food distribution, and industrial parts industries. Gezeta is a certified senior consultant in the production, distribution, tools, and financial modules.

Before his Epicor consulting career with Tomerlin-ERP, Steve was a Senior Development Lead for Cricket Communications leading numerous business initiative implementations and system integrations for mycricket. He was responsible for estimates, design, team management, implementation, defect management, and critical production issue support triage and resolution.

Dwayne is a dedicated business problem solver. Dwayne has built custom solutions for a vast array of industries including aerospace, automotive and apparel. Dwayne has been recognized for his willingness to tackle the toughest and most complex issues.