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Matrix Metalloproteinase-2 (MMP-2) and-9 (MMP-9) Gene Variants and Microvascular Complications in Type 2 Diabetes
Jelic M Andjelic1, D Radojkovic2, A Nikolic2
1Department of Endocrinology, Diabetes and Metabolic Diseases, Clinical Medical Centre Zvezdara, Belgrade, Serbia.
Abstract:
Vascular complications are the leading cause of increased morbidity and mortality of diabetic patients. It has been postulated that matrix metalloproteinases MMP-2 and MMP-9, zinc-dependent endopeptidases through remodeling of the extracellular matrix, can contribute to the onset and progression of diabetic vascular complications. The aim of our study was to assess whether there is a major difference in single nucleotide polymorphisms in the MMP-2 (at position -1306C˃T) and MMP-9 (at position -1562C˃T) gene in type 2 diabetic patients and healthy controls and to determine whether there is an association of these gene variants with the presence of microvascular complications in diabetic patients. Our study included 102 type 2 diabetes patients and a control group which was comprised of 56 healthy controls. All diabetic patients were screened for microvascular diabetes complications. Genotypes were detected by polymerase chain reactions followed by restriction analyses with specific endonucleases and their frequencies were determined. The MMP-2 variant -1306C>T showed a negative correlation with type 2 diabetes (p=0.028). It was also shown that the presence of the -1306C allele increases the probability of developing type 2 diabetes. This was a 2.2 fold increase and that the -1306 T allele has a protective role in regards to type 2 diabetes. The MMP-2 variant -1306T showed a negative correlation with diabetic polyneuropathy (p=0.017), meaning that allele-1306T has a protective role in regards to diabetic polyneuropathy while the presence of allele -1306C increases the probability of developing diabetic polyneuropathy by 3.4 fold. Our study showed that the MMP-2 gene variant (-1306C) doubles the risk of developing type 2 diabetes, and for the first time an association of this gene variant and the presence of diabetic polyneuropathy was shown.
Insights
Genetic variants in the matrix metalloproteinase-2 (MMP-2) gene are linked to type 2 diabetes and its complications. The -1306C allele increases diabetes risk, while the -1306T allele shows a protective effect against diabetes and diabetic polyneuropathy.
Area of Science:
- Genetics
- Molecular Biology
- Endocrinology
Background:
- Vascular complications significantly increase morbidity and mortality in diabetic patients.
- Matrix metalloproteinases (MMPs), specifically MMP-2 and MMP-9, are implicated in extracellular matrix remodeling and may contribute to diabetic vascular disease.
- Single nucleotide polymorphisms (SNPs) in MMP genes are potential factors in the development of diabetes and its complications.
Purpose of the Study:
- To investigate differences in MMP-2 (-1306C>T) and MMP-9 (-1562C>T) gene polymorphisms between type 2 diabetes patients and healthy controls.
- To determine the association between these MMP gene variants and the presence of microvascular complications in type 2 diabetes.
Main Methods:
- Genotyping of 102 type 2 diabetes patients and 56 healthy controls using polymerase chain reaction and restriction analyses.
- Screening of diabetic patients for microvascular complications.
- Statistical analysis of genotype frequencies and their correlation with diabetes and complications.
Main Results:
- The MMP-2 -1306C>T variant showed a negative correlation with type 2 diabetes (p=0.028).
- The -1306C allele of MMP-2 was associated with a 2.2-fold increased probability of developing type 2 diabetes, while the -1306T allele demonstrated a protective effect.
- The MMP-2 -1306T variant was negatively correlated with diabetic polyneuropathy (p=0.017), indicating a protective role, whereas the -1306C allele increased the risk by 3.4-fold.
Conclusions:
- The MMP-2 gene variant -1306C significantly increases the risk of developing type 2 diabetes, approximately doubling it.
- This study provides the first evidence linking the MMP-2 -1306C/T gene variant to the presence of diabetic polyneuropathy.
- Targeting MMP-2 pathways could be a potential strategy for managing type 2 diabetes and its vascular complications.
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