Abstract
Introduction . Diabetes mellitus is one of the most common diseases in the world. In 4–25 % of patients with this pathology, diabetic foot syndrome develops, leading to a large number of amputations accompanied by postoperative mortality. Aim . To assess the relationship of polymorphisms of the VEGFA 634 C˃G and MMP9 8202 A˃G genes with markers of endothelial dysfunction and state of the microvasculature in diabetes mellitus. Materials and methods . In 198 people with uncomplicated diabetes mellitus and 199 people with diabetic feet, polymorphisms 634 C˃G of the VEGFA gene and 8202 A˃G of the MMP9 gene were studied by polymerase chain reaction. The content of endothelin 1, NO 2 and NO 2 – /NO 3 – , MMP 9 and state of microcirculation at three points were studied by laser Doppler flowmetry in 30 people from each group, comparable in frequency of the indicated gene polymorphisms. Results . The frequency of polymorphisms of genes VEGFA 634 C˃G, MMP9 8202 A>G did not differ in the groups of patients. In diabetic feet, a decrease in the total perfusion index by 1.4, 1.8 and 1.5 times was recorded at three points. At a point on the forearm with a diabetic foot, a 1.6-fold decrease in the temporal variability of perfusion was revealed; at the dorsum and first toe of the foot, a decrease in the coefficient of variation by 1.7 and 1.5 times was revealed. In patients with different variants of the course of diabetes mellitus, there were no differences in the levels of endothelin-1, NO 2 and NO 2 – / NO 3 – , MMP 9. Conclusion . Polymorphisms of the VEGFA 634 C˃G, MMP9 8202 A˃G genes in different variants of the course of3 – diabetes mellitus correlate with indicators of general state of the microvasculature. The parallelism of changes in the content of endothelin 1, MMP 9 and polymorphic variants of the MMP9 8202 A˃G gene indicates a deep remodeling of the vasculature, which may be an important link in the pathogenesis of the development of complications of diabetes mellitus.
Highlights
ConclusionPolymorphisms of the VEGFA 634 CG, MMP9 8202 AG genes in different variants of the course of diabetes mellitus correlate with indicators of general state of the microvasculature
The parallelism of changes in the content of endothelin 1, MMP 9 and polymorphic variants of the MMP9 8202 AG gene indicates a deep remodeling of the vasculature, which may be an important link in the pathogenesis of the development of complications of diabetes mellitus
Correlation of polymorphisms of VEGFA 634 CG, MMP9 8202 AG genes with indicators of the state of the microvasculature in diabetic foot syndrome
Summary
Polymorphisms of the VEGFA 634 CG, MMP9 8202 AG genes in different variants of the course of diabetes mellitus correlate with indicators of general state of the microvasculature. По данным литературы [6, 7], полиморфные варианты гена VEGFA, кодирующего выработку сосудистого эндотелиального фактора роста А, участвую щего процессе ремоделирования сосудистой стенки, ассоциированы с развитием сахарного диабета, при этом данных о связи данного гена с развитием синдрома диабетической стопы нет. Исследование включало в себя три этапа: 1-й этап – определение полиморфизмов 634 CG гена VEGFA и 8202 AG гена MMP9 в клинических группах больных; 2-й этап – исследование состояния микроциркуляторного русла, маркеров дисфункции эндотелия у 30 больных с неосложненным течением сахарного диабета и 30 пациентов с развитием синдрома диабетической стопы, сопоставимых по частоте распределения полиморфизмов гена VEGFA 634 CG и гена MMP9 8202 AG с полученными ранее данными; 3-й этап – оценка взаимосвязи между полиморфизмами исследуемых генов и показателями микроциркуляции, маркерами дисфункции эндотелия в группах больных. Microcirculation indicators for various variants of the course of diabetes mellitus (Me (25th; 75th))
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