Two MMP-2 Promoter Polymorphisms (–790T/G and –735C/T) in Chronic Heart Failure

Abstract

Remodelling of extracellular matrix by activated matrix metalloproteinases is considered to contribute to progression of ventricle remodelling during chronic heart failure. The aim of this study was to associate two promoter polymorphisms, -790T/G and -735C/T, in the gene for matrix metalloproteinase (MMP)-2 (gelatinase A) with chronic heart failure (CHF). For this purpose, 164 patients (124 men, 40 women, median age 56 years, range 21-91 years) with CHF (functional class NYHA II-IV, ejection fraction median 25%, cardiothoracic index more than 50%) were compared with 196 control subjects without clinical signs of cardiovascular disease (131 men and 65 women, median age 56 years, range 27-84 years) in -790T/G and -735C/T MMP-2 genotype distributions and allelic frequencies. The genotypes were determined by polymerase chain reaction (PCR) with restriction analyses. A significant increase of the T allele of the -790T/G MMP-2 polymorphism (p = 0.04), as well as of the C allele of the -735C/T MMP-2 gene polymorphism, in patients with CHF was proven (p = 0.04). The heterozygote CT of the -735C/T MMP-2 polymorphism exhibits a 7 times higher odds ratio (OR) for the CHF patients with lower levels of total cholesterol (less than 5 mmol/l), especially for non-hypertensive CHF men (OR = 7.28, 95% confidence interval 1.51-35.03, p = 0.006). Determination of MMP polymorphisms in the regulatory area of the gene could help us to comprehend individual susceptibility of patients with CHF to MMP inhibitors based on known risks of MMP genotypes.

No Association of Matrix Metalloproteinase [MMP]-2 (−735C > T) and Tissue Inhibitor of Metalloproteinase [TIMP]-2 (−418G > C) Gene Polymorphisms with Cervical Cancer Susceptibility

“…Contrarily Vasku et al [18] had found that variant allele frequency of the -735C [ T MMP-2 polymorphism was significantly higher in patients with chronic heart failure than in subjects without clinical signs of cardiovascular disease. Cotignola et al [19] reported patients with esophageal squamous cell carcinoma carrying the -735CC genotypes had an increased risk of developing cancer.…”

Genetic variation of MMP‐2(‐735 C>T) and MMP‐9(‐1562 C>T) gene in risk of development of HAND and severity of HAND

“…The MMP‐2 and MMP‐9 polymorphisms (−735C > T) and (−1562C > T) were genotyped in subjects using polymerase chain reaction (PCR)‐restriction fragment length polymorphism. Primers for amplification of MMP‐1 (−1607 2G > 1G) and MMP‐3 (−1612 5 A > 6 A) were taken as described previously . PCR was performed in a total volume of 25 μl with 15 pmol of each primer, genomic DNA (100–150 ng), 10 mM deoxynucleotide triphosphates, PCR buffer containing 100 mM Tris–HCl (pH 8.6), 50 mM KCl, 1.5 mM MgCl 2 and 1.5 units of Taq polymerase (Bangalore Genei, Bengaluru, India).…”

Matrix Metalloproteinases in Myocardial Infarction and Heart Failure

“…39 Similarly, the −790 T/G MMP-2 polymorphism, in addition to the −735 C/T polymorphism, also associates with chronic heart failure in patients from the Czech Republic. 40 How these polymorphisms effect heart failure related deaths is still unclear.…”