Relationship of polymorphisms in the tissue inhibitor of metalloproteinase (TIMP)-1 and -2 genes with chronic heart failure

Abstract

Dysregulated expression of tissue inhibitors of matrix metalloproteinases (TIMPs) is associated with systolic dysfunction and worsening heart failure (HF). However, no study has assessed the relationship between TIMP polymorphisms and chronic HF. In this study, 300 HF outpatients with reduced left ventricular ejection fraction and 304 healthy blood donors were genotyped for the 372 T > C polymorphism (Phe124Phe; rs4898) in the TIMP-1 gene and the −418 G > C polymorphism (rs8179090) in the TIMP-2 gene to investigate whether these polymorphisms are associated with HF susceptibility and prognosis. The genotype and allele frequencies of the 372 T > C polymorphism in HF patients were not significantly different from those observed among healthy subjects, and the C allele of the −418 G > C polymorphism was very rare in our population (frequency < 1%). After a median follow-up duration of 5.5 years, 121 patients (40.3%) died (67 of them from HF). Survival analysis did not show statistically significant differences in all-cause death and HF-related death between patients with and without the T allele (P > 0.05 for all comparisons). Thus, our findings do not support the hypothesis that the 372 T > C (Phe124Phe) polymorphism in the TIMP-1 gene and the −418 G > C polymorphism in the TIMP-2 gene are associated with HF susceptibility and prognosis in Southern Brazilians.

TIMP2 Polymorphisms Association With Curve Initiation and Progression of Thoracic Idiopathic Scoliosis in the Caucasian Females

“…34,35 Variations in the TIMP2 DNA sequence have been associated with differing pathogeneses of many diseases, such as chronic obstructive pulmonary disease, 36 aortic aneurysms, 37 neoplasms, 35 and differing types of muscle-related conditions. [38][39][40][41] Our study was consistent with works by Jiang et al 21 and Ogura et al 22 as we also did not find any differences across our IS and non-IS groups for rs8179090. However, we could not confirm the relationship of this polymorphism with Cobb angle curvature, which could be explained by several aspects of our analysis.…”

“…The C allele has been confirmed associate with reduced transcription activity leading to lower TIMP2 gene expression due to changing consensus sequence affinity to Sp1 transcription factor binding site . Variations in the TIMP2 DNA sequence have been associated with differing pathogeneses of many diseases, such as chronic obstructive pulmonary disease, aortic aneurysms, neoplasms, and differing types of muscle‐related conditions …”

The Pathogenesis of Cardiac Fibrosis: A Review of Recent Progress

“…All four known TIMPs are expressed in the heart, predominantly produced by CFs but also a variety of other cell types. TIMP expression is correlated with cardiac diseases [ 40 , 41 , 42 , 43 , 44 ].…”

The Effect of Maximal Exercise on Matrix Metalloproteinase, its Inhibitor (MMP9 and TIMP1), and the Role of MMP9 -1562 C/T and TIMP1 372 T/C Polymorphisms

“…According to the ndings of this study, the TIMP1 372 T/C polymorphism had a genetic role in hypertension. Polina, Araújo [31] studied 300 individuals with chronic heart disease and 304 healthy individuals and found that the genotype and allele frequencies of the TIMP1 372 T/C polymorphism in the patient group were not different from the healthy group. When the ndings of the current study were evaluated in terms of atherosclerosis risk factors, it can be stated that the individuals with the C allele are in the higher risk group than individuals with the T allele as a result of the differences in TC and LDL-C levels in the allele groups.…”