Dataset Information

Matrix Metalloproteinase-2 Polymorphisms in Chronic Heart Failure: Relationship with Susceptibility and Long-Term Survival.

ABSTRACT: Circulating levels of matrix metalloproteinase-2 (MMP-2) predict mortality and hospital admission in heart failure (HF) patients. However, the role of MMP-2 gene polymorphisms in the susceptibility and prognosis of HF remains elusive. In this study, 308 HF outpatients (216 Caucasian- and 92 African-Brazilians) and 333 healthy subjects (256 Caucasian- and 77 African-Brazilians) were genotyped for the -1575G>A (rs243866), -1059G>A (rs17859821), and -790G>T (rs243864) polymorphisms in the MMP-2 gene. Polymorphisms were analyzed individually and in combination (haplotype), and positive associations were adjusted for clinical covariates. Although allele frequencies were similar in HF patients and controls in both ethnic groups, homozygotes for the minor alleles were not found among African-Brazilian patients. After a median follow-up of 5.3 years, 124 patients (40.3%) died (54.8% of them for HF). In Caucasian-Brazilians, the TT genotype of the -790G>T polymorphism was associated with a decreased risk of HF-related death as compared with GT genotype (hazard ratio [HR] = 0.512, 95% confidence interval [CI] 0.285-0.920). However, this association was lost after adjusting for clinical covariates (HR = 0.703, 95% CI 0.365-1.353). Haplotype analysis revealed similar findings, as patients homozygous for the -1575G/-1059G/-790T haplotype had a lower rate of HF-related death than those with any other haplotype combination (12.9% versus 28.5%, respectively; P = 0.010). Again, this association did not remain after adjusting for clinical covariates (HR = 0.521, 95% CI 0.248-1.093). Our study does not exclude the possibility that polymorphisms in MMP-2 gene, particularly the -790G>T polymorphism, might be related to HF prognosis. However, due to the limitations of the study, our findings need to be confirmed in further larger studies.

SUBMITTER: Beber AR

PROVIDER: S-EPMC4995023 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Publications

Matrix Metalloproteinase-2 Polymorphisms in Chronic Heart Failure: Relationship with Susceptibility and Long-Term Survival.

Beber Ana Rubia C AR Polina Evelise R ER Biolo Andréia A Santos Bruna L BL Gomes Daiane C DC La Porta Vanessa L VL Olsen Virgílio V Clausell Nadine N Rohde Luis E LE Santos Kátia G KG

PloS one 20160823 8

Circulating levels of matrix metalloproteinase-2 (MMP-2) predict mortality and hospital admission in heart failure (HF) patients. However, the role of MMP-2 gene polymorphisms in the susceptibility and prognosis of HF remains elusive. In this study, 308 HF outpatients (216 Caucasian- and 92 African-Brazilians) and 333 healthy subjects (256 Caucasian- and 77 African-Brazilians) were genotyped for the -1575G>A (rs243866), -1059G>A (rs17859821), and -790G>T (rs243864) polymorphisms in the MMP-2 gen ...[more]

PMID: 27551966

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Project description:In cardiovascular disorders, the myocardium may be subjected to the breakdown and remodeling of collagen by metalloproteinase-9 (MMP-9). We hypothesized that the serum MMP-9 concentration may be elevated in pediatric patients with rheumatic heart disease (RHD) and heart failure (HF), and its level can be correlated with the HF severity. Thus, in the present study, we aimed to evaluate the sensitivity and accuracy of MMP-9 to predict HF in children with RHD and to determine its effectiveness as an indicator of the degree of HF. This study included 98 consecutive children admitted to the Department of Pediatrics, Zagazig University Hospital, Al Sharqia Governorate, Egypt with newly diagnosed RHD. Their ages ranged from 8.5 to 16 years. Fifty-eight children had RHD without HF while 40 children were complicated with HF which was diagnosed clinically and by echocardiography. A total of 44 healthy children were enrolled as a control group. MMP-9 serum levels were estimated by enzyme-linked immunosorbent assay. The serum MMP-9 concentration was higher in the RHD without HF and RHD with HF groups than this level noted in the control (P<0.001). MMP-9 was a significant predictor of HF; area under the curve (AUC)=0.85 [95% confidence interval (CI), 0.76-0.94]. At the level of 386.9 ng/ml, MMP-9 detected HF with a sensitivity 95% (95% CI, 83.08-99.39), specificity 74.14% (95% CI, 60.96-84.74), positive predictive value 71.70% (95% CI, 61.96-79.75), negative predictive value 95.56% (95% CI, 84.67-98.82) and accuracy 82.65% (95% CI, 73.69-89.56). In addition, MMP-9 showed a significant negative correlation with ejection fraction and fractional shortening (P=0.01 and P=0.02, respectively). In conclusion; MMP-9 may be an independent sensitive marker with which to detect HF in children with RHD and it can predict the prognoses of these patients as it correlates with the severity of HF. Further studies considering MMP-9 in the detection of 'silent' RHD in school aged children and asymptomatic HF in children with known RHD especially in rural areas, are highly recommended.

Dataset Information

Matrix Metalloproteinase-2 Polymorphisms in Chronic Heart Failure: Relationship with Susceptibility and Long-Term Survival.

Publications

Matrix Metalloproteinase-2 Polymorphisms in Chronic Heart Failure: Relationship with Susceptibility and Long-Term Survival.

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