Biochemical and Biophysical Research Communications
Genetic polymorphism c.1562C>T of the MMP-9 is associated with macroangiopathy in type 2 diabetes mellitus
Introduction
Type 2 diabetes mellitus (T2DM) is strongly associated with elevated mortality and morbidity from atherosclerotic vascular disease manifesting as coronary heart disease, cerebrovascular disease, and peripheral vascular disease [1], [2]. Diabetic macroangiopathy, manifested by atherosclerosis of coronary arteries, cerebral arteries, and large arteries of the lower extremities, is the major cause of mortality and significant morbidity [3]. Predictors of susceptibility for development of macroangiopathy in diabetic subjects would help focus our treatment strategies.
Matrix metalloproteinase-9 (MMP-9) is one of a set of zinc-dependent endopeptidases capable of degrading components of the extracellular matrix (ECM) [4]. The MMP-9 gene has a C-to-T promoter polymorphism at position −1562, which affects transcription and leads to promoter low-activity (C/C) and high-activity (C/T, T/T) genotypes [5]. MMP-9 has three repetitive type II fibronectin domains, which allow it to bind to ECM components, such as gelatin, collagen, and laminin. Increased expression of this enzyme is seen in some neoplastic, cardiovascular, and respiratory diseases [6]. Recent studies revealed that the plasma level of MMP-9 was of both diagnostic and prognostic significance in coronary artery diseases and renal diseases [7], [8], [9], [10]. MMP-9 has recently been identified in human atherosclerotic lesions [11], [12]. It is active against denatured collagens and type IV, V, and XI collagens in addition to the proteoglycans and elastin also found in atherosclerotic lesions [13], [14].
No data are as yet available on the impact of the MMP-9 genotypes at the vessel-wall level in respect to the atherosclerotic plaque rupture and thrombosis. Nor has it hitherto been sought to establish whether MMP-9 genotypes affect development and progression of diabetic macroangiopathy. In the present study, we investigated the association between MMP-9 c.1562C>T polymorphism and the macroangiopathy in T2DM.
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Materials and methods
Study subjects. The study was approved by the Clinical Research Ethics Committee of Harbin Medical University, and all subjects gave written informed consent. Macroangiopathy was diagnosed by the presence of cardiovascular disease or cerebrovascular disease and peripheral vascular disease. Cardiovascular disease was defined as a history of myocardial infarction, angina pectoris or ischemic heart disease, ongoing treatment with drugs prescribed for cardiovascular disease, or the presence of a
Association of the MMP-9 c.1562C>T polymorphism with diabetic macroangiopathy
The relationship between distribution frequency of genotypes and alleles of MMP-9 was shown in Table 1. The genotype frequency of the c.1562C>T polymorphism of the MMP-9 gene were as follows: the genotype (CC, CT, and TT) distribution of c.1562C>T polymorphism of the MMP-9 gene was 60.0%, 31.3%, and 8.8% in diabetic patients with macroangiopathy, 76.3%, 21.3%, and 2.5% in diabetic patients without macroangiopathy, and 77.5%, 21.3%, and 1.3% in controls, respectively. The genotype frequency for
Discussion
In the present study, we raised the question of whether the polymorphism of the MMP-9 gene may be associated with diabetic macroangiopathy. Specifically, we hypothesized that the allele frequencies of the different polymorphisms in diabetic patients might be different from those in nondiabetic subjects and that the different polymorphisms could be related to various forms of macroangiopathy and its risk factors in patients with type 2 diabetes. Our results suggested that genetic polymorphism
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These authors contributed equally to this study.