基质金属蛋白酶-2 (MMP-2)和9 (MMP-9)基因变异与2型糖尿病患者微血管并发症

IF 0.5 4区 医学 Q4 GENETICS & HEREDITY Balkan Journal of Medical Genetics Pub Date : 2022-06-01 DOI:10.2478/bjmg-2022-0001
Jelic M Andjelic, D Radojkovic, A Nikolic, Lj Rakicevic, T Babic, D Jelic, N M Lalic
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引用次数: 0

摘要

血管并发症是糖尿病患者发病率和死亡率增加的主要原因。基质金属蛋白酶MMP-2和MMP-9是锌依赖性内肽酶,通过重塑细胞外基质,参与糖尿病血管并发症的发生和发展。本研究的目的是评估2型糖尿病患者和健康对照中MMP-2 (-1306C位点)和MMP-9 (-1562C位点)基因的单核苷酸多态性是否存在主要差异,并确定这些基因变异是否与糖尿病患者微血管并发症存在关联。我们的研究包括102名2型糖尿病患者和一个由56名健康对照者组成的对照组。所有糖尿病患者均接受微血管糖尿病并发症筛查。用聚合酶链反应检测基因型,然后用特定的内切酶进行限制性内切分析,确定基因型的频率。MMP-2变异-1306C>T与2型糖尿病呈负相关(p=0.028)。研究还表明,-1306C等位基因的存在增加了患2型糖尿病的可能性。这是2.2倍的增长,并且-1306 T等位基因对2型糖尿病有保护作用。MMP-2变异-1306T与糖尿病多发神经病变呈负相关(p=0.017),说明等位基因-1306T对糖尿病多发神经病变具有保护作用,而等位基因-1306C的存在使糖尿病多发神经病变的发生概率增加3.4倍。我们的研究表明,MMP-2基因变异(-1306C)使2型糖尿病的发病风险增加一倍,并且首次发现该基因变异与糖尿病多发神经病变存在关联。
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Matrix Metalloproteinase-2 (MMP-2) and-9 (MMP-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 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.

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期刊介绍: Balkan Journal of Medical Genetics is a journal in the English language for publication of articles involving all branches of medical genetics: human cytogenetics, molecular genetics, clinical genetics, immunogenetics, oncogenetics, pharmacogenetics, population genetics, genetic screening and diagnosis of monogenic and polygenic diseases, prenatal and preimplantation genetic diagnosis, genetic counselling, advances in treatment and prevention.
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