Association of MMP-2 and MMP-9 Polymorphisms with Diabetes and Pathogenesis of Diabetic Complications

Abstract

Type 2 diabetes mellitus (T2D) affects millions of people around the world, and its complications have serious health consequences. In addition to external factors, the causes of morbidity and increased risk were also sought in the variability of the human genome. A phenomenon that can answer these questions is the occurrence of single-nucleotide polymorphisms (SNP). They constitute a field for research into genetic determinants responsible for the increase in the risk of the discussed metabolic disease. This article presents the outline of two enzymes: metalloproteinases 2 and 9 (MMP-2, MMP-9), their biological activity and the effect caused by differences in individual alleles in the population, as well as the reports on the importance of these DNA sequence variations in the occurrence of diabetes mellitus type 2 and associated conditions. The results of the conducted research indicate a relationship between two MMP-2 polymorphisms (rs243865, rs243866) and two MMP-9 polymorphisms (rs3918242, rs17576) and the presence of T2D. This could offer a promising possibility to use them as predictive and diagnostic markers. However, due to the low number of reports, more research is needed to clearly confirm the link between these SNPs and diabetes.

Keywords: diabetes; metalloproteinase 2; metalloproteinase 9.

Figure 1

Diagram of the domain structure of (A) gelatinase-A (MMP-2) and (B) gelatinase-B (MMP-9). Created with BioRender.com.

Figure 2

Diagram of the gelatinase action process in the processes of tumor metastasis. (A) Hydrolysis of α chains collagen bonds in collagen IV triple-helix building the basement membrane. (B) Degradation of the protein components of the extracellular matrix. (C) Catalysis of the components of the basement membrane and extracellular matrix causes their degradation and enables the migration of cancer cells through the epithelium to the blood vessels from where they move around the body, finally creating secondary cancers in the sites of metastasis. (D) Gelatinases have a positive effect on the tumor angiogenesis processes. Created with BioRender.com.