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.

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.