title: 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.
authors.affiliation: Laboratory of Human Molecular Genetics, Universidade Luterana do Brasil, Canoas, RS, Brazil.
authors.forename: Ana Rubia C
authors.initials: AR
authors.lastname: Beber
authors.affiliation: Laboratory of Human Molecular Genetics, Universidade Luterana do Brasil, Canoas, RS, Brazil.
authors.forename: Evelise R
authors.initials: ER
authors.lastname: Polina
authors.affiliation: Experimental and Molecular Cardiovascular Laboratory and the Heart Failure and Cardiac Transplant Unit, Cardiology Division, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil.
authors.forename: Andréia
authors.initials: A
authors.lastname: Biolo
authors.affiliation: Laboratory of Human Molecular Genetics, Universidade Luterana do Brasil, Canoas, RS, Brazil.
authors.forename: Bruna L
authors.initials: BL
authors.lastname: Santos
authors.affiliation: Laboratory of Human Molecular Genetics, Universidade Luterana do Brasil, Canoas, RS, Brazil.
authors.forename: Daiane C
authors.initials: DC
authors.lastname: Gomes
authors.affiliation: Experimental and Molecular Cardiovascular Laboratory and the Heart Failure and Cardiac Transplant Unit, Cardiology Division, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil.
authors.forename: Vanessa L
authors.initials: VL
authors.lastname: La Porta
authors.affiliation: Experimental and Molecular Cardiovascular Laboratory and the Heart Failure and Cardiac Transplant Unit, Cardiology Division, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil.
authors.forename: Virgílio
authors.initials: V
authors.lastname: Olsen
authors.affiliation: Experimental and Molecular Cardiovascular Laboratory and the Heart Failure and Cardiac Transplant Unit, Cardiology Division, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil.
authors.forename: Nadine
authors.initials: N
authors.lastname: Clausell
authors.affiliation: Experimental and Molecular Cardiovascular Laboratory and the Heart Failure and Cardiac Transplant Unit, Cardiology Division, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil.
authors.forename: Luis E
authors.initials: LE
authors.lastname: Rohde
authors.affiliation: Laboratory of Human Molecular Genetics, Universidade Luterana do Brasil, Canoas, RS, Brazil.|Experimental and Molecular Cardiovascular Laboratory and the Heart Failure and Cardiac Transplant Unit, Cardiology Division, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil.
authors.forename: Kátia G
authors.identifier: http://orcid.org/0000-0001-5231-2071
authors.initials: KG
authors.lastname: Santos
mesh_terms: D000368:Aged; D000483:Alleles; D015415:Biomarkers; D001938:Brazil; D015897:Comorbidity; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006333:Heart Failure / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D016016:Proportional Hazards Models; D012307:Risk Factors
chemical_list: D015415:Biomarkers; D020778:Matrix Metalloproteinase 2