Endocrine Abstracts

Background: Vascular complications are leading cause of increased morbidity and mortality of diabetic patients. Pathophysiological mechanisms included in the development and progression of diabetic complications are various and lately it has been postulated that matrix metalloproteinases MMP-2 and MMP-9, zinc-dependent endopeptidases through remodeling of 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 association of these gene variants with the presence of microvascular complications in diabetic patients.

Methods: Our study included 102 type 2 diabetes patients and control group which comprised 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 (PCR-RFLP) and their frequencies determined.

Results: MMP-2 gene variant -1306C>T showed negative correlation with the presence of T2DM (P=0.042). It was shown that presence of allele -1306C increases the probability of developing type 2 diabetes 2.1 times and that allele -1306 T has protective role regarding type 2 diabetes. MMP-2 variant -1306T showed negative correlation with diabetic polyneuropathy (P=0.017) which means that allele-1306T has protective role regarding diabetic polyneuropathy while presence of allele -1306C increases the probability of developing diabetic polyneuropathy 3.2 fold.

Conclusion: To our knowledge, this is the first study investigating MMP2 and MMP9 genetic variants and all three microvascular complications. Our study showed that MMP-2 gene variant (-1306C) doubles the risk of developing type 2 diabetes and for the first time showed association of this gene variant and presence of diabetic polyneuropathy.

Keywords: diabetes mellitus, matrix metalloproteinase-2 and -9, SNP (single nucleotide polymorphism), microvascular complications, diabetic polyneuropathy.