<abstract xmlns="http://www.w3.org/1999/xhtml">

<p>Vascular complications are the leading cause of increased morbidity and mortality of diabetic patients. It has been postulated that matrix metalloproteinases <italic>MMP-2</italic> and <italic>MMP-9</italic>, 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 <italic>MMP-2</italic> (at position -1306C˃T) and <italic>MMP-9</italic> (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 <italic>MMP-2</italic> 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 <italic>MMP-2</italic> 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 <italic>MMP-2</italic> 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.</p></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.

Matrix metalloproteinase-2 (<italic>MMP-2</italic> ) and-9 (<italic>MMP-9</italic>) gene variants and microvascular complications in type 2 diabetes patients

Balkan Journal of Medical Genetics

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Matrix metalloproteinase-2 ( ) and-9 () gene variants and microvascular complications in type 2 diabetes patients

Vascular complications are the leading cause of increased morbidity and mortality of diabetic patients. It has been postulated that matrix metalloproteinases...

Genotype	Patients n (%)	Controls n ( %)	p-value or (95 % CI)
-1306CC	22 (75.86)	27 (48.21)	0.0170٭
-1306TC and -1306TT	7 (24.14)	29 (51.79)	0.2962 (0.1091-0.8045)

Genotype	Patients n (%)	Controls n (%)	P-value OR (95 % CI) patients vs. control *
MMP-2
-1306CC	53 (67.1)	27 (48)	0.028
-1306CT	24 (30.4)	25 (45)	0.457 (0.226-0.932)
-1306TT	2 ( 2.5)	4 (7)

MMP-9
-1562CC	56 (71)	40 (71)	0.945
-1562CT	20 (25)	16 (29)	1.27 (0.482-2.187)
-1562TT	3 (4)	0 (0)

Variable	Values
Age, mean± SD	61.4 ± 7.3
Gender, male n (%) female n ( %)	65 (63.7) 37 (36.3)
Smokers, n (%)	23 (22.5)
Diabetes duration, mean± SD	10.1±5.8
BMI, mean± SD	28.8±4.8
HbA1c, mean± SD	9.40±2.22
FBG, mean± SD	6.90±1.94
Total cholesterol (mmol/l), mean± SD	5.20±1.35
LDLc (mmol/l), mean± SD	3.11±1.03
HDLc (mmol/l), mean± SD	1.15±0.30
Triglycerides (mmol/l), mean± SD	2.25±1.16
Albumin mg/24h/urine, mean± SD	12.54±2.79
Serum creatinine (μmol/l), mean± SD	87.81±42.75
OAD only, n (%)	23 (22.5)
Insulin only, n (%)	14 (13.7)
OAD + insulin, n (%)	65 (63.7)
Metformin, n (%)	88 (86.3)
Retinopathy non-proliferative, n (%)	21 (20.6)
Retinopathy proliferative, n (%)	9 (8.8)
Polyneuropathy, n (%)	40 (39.2)
Nephropathy, n (%)	11 (10.8)

Matrix metalloproteinase-2 (MMP-2 ) and-9 (MMP-9) gene variants and microvascular complications in type 2 diabetes patients

Article Category: Original Article

Publicado en línea: 01 mar 2023

Páginas: 35 - 40

DOI: https://doi.org/10.2478/bjmg-2022-0001

© 2022 Andjelic Jelic M, Radojkovic D, Nikolic A, Rakicevic Lj, Babic T, Jelic D, Lalic NM, published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Correlation of the MMP-2 variant -1306T with the presence of diabetic polyneuropathy.

Genotype distrubution of the MMP-2 and MMP-9 gene variants in patients with diabetes and in the control group.

Demographic and clinical characteristics of patients.