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CYTOKINE REGULATION MARKERS OF OSTEOMETABOLISM AND GENE POLYMORPHISM OF MATRIX METALLOPROTEINASE-9 836AG (RS17576) IN CHILDREN OF THE STRONTIUM GEOCHEMICAL PROVINCE

Н.В. Зайцева, Ksenia Starkova, Оleg V. Dolgikh, В. А. Алексеев, Konstantin Luzhesky

Abstract

The specificity of the microelement environment in the population of individual geochemical provinces determines the features of homeostasis regulation processes. In conditions of excessive intake of strontium with drinking water, it is assumed pathological disorders of the parameters of osteometabolism with the involvement of immune regulation mechanisms. We examined 59 children of preschool age permanently residing in the territory of the strontium geochemical province and consuming drinking water with an excess of strontium. The comparison group consisted of children consuming drinking water with an acceptable strontium content. The strontium concentration in the blood was investigated by inductively coupled plasma mass spectrometry. Cytokine markers were determined by enzyme immunoassay. Genotyping was performed by real-time polymerase chain reaction. Excessive levels of strontium in the blood of children of the observation group were revealed, simultaneously associated with an increased content of ionized Ca2+. Changes in the system of cytokine regulatory mechanisms were shown with a 3.47-fold increase in TNFalfa, a 1.51-fold decrease in osteoprotegerin and an imbalance in the RANKL/osteoprotegerin system (p<0.05). Genetic analysis of candidate gene polymorphism established in children of the main group an increased (by 2.55 times) frequency relative to the comparison group of the variant G allele of the MMP9 836A>G gene of matrix metalloproteinase-9 (OR=3.48; 95% Cl=1.44-8.43), which regulates the binding of calcium and hydroxyapatites of the extracellular matrix and the expression of proinflammatory mediators. A significant increase in RANKL was revealed by 1.83 times in carriers of the G allele of MMP9 836A>G, which indicates the participation of MMP9 in the development of pathological changes in conditions of imbalance of strontium-calcium interaction, activation of bone resorption processes, mediated by increased expression of proinflammatory cytokine mediators, and the formation in the child population of strontium geochemical province, consuming drinking water with an excess of strontium, specific strontium ossification.

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