The Relationship of Molecular-Genetic Markers of Chemokines with Clinical Manifestations of Chronic Kidney Disease

Author Name(s): *Elena V. Nekipelova, Olga N. Novakova, Tatyana I. Yakunchenko, Mikhail I. Churnosov, Nina I. Zhernakova, Vladimir F. Kulikovskiy
Author Email: litovkina@bsu.edu.ru

Abstract

The article presents the results of studying the relationship of polymorphic variants of chemokine genes (1931A/T CCL4, A/G CXCL11 (rs4512021), -403A/G CCL5, C/G CCL2 (rs2857657), -801G/A CXCL12) with the features of clinical manifestations of chronic glomerulonephritis. It was revealed, that the allele-801 A CXCL12 (OR = 1.85, p = 0.04) was the marker for the development of hematuric form of chronic glomerulonephritis.

Introduction

Chronic glomerulonephritis (CGN) is one of the most common chronic kidney diseases, which come to death of patients, due to the development of renal failure (Wada et al., 2008; Litovkina et al., 2014). Despite the relatively low prevalence of CGN in population, the progressive course of disease is the reason why patients with chronic glomerulonephritis are the main contingent of nephrology departments, hemodialysis and kidney transplantation (Nekipelova et al., 2016). The progression of nephritis and the development of renal failure depend on the activity of the process, which is not always clinically evident. Due to this, CGN is often diagnosed for the first time at the terminal stage of chronic kidney disease.

Platelets and neutrophils play a major role among the cellular mediators of immune destruction of the glomerular renal apparatus, including CGN (Woerkom et al., 2000). Their number in leukocyte infiltration depends on the concentration of tumor necrosis factors, interleukins and chemokines, which induce respiratory explosion of neutrophilic granulocytes. It should also be noted, that among the cytokines, chemokines occupy a special place in the development of immune-inflammatory reactions in case of chronic glomerulonephritis. They are produced by immunocompetent cells, infiltrating the glomerular zone and the interstitial space of damaged nephrons (Wada, 2008; Azmandian et al., 2012). According to the literature data, such chemokines as monocyte chemotactic protein-1 (CCL2) and CCL5-factor, regulating the activation of normal T-cell expression and secretion, play an important role in the pathogenesis of CGN (Lin et al., 2009).

Therefore, further investigations, aimed at studying the mechanisms of emergence, development and progression of chronic glomerulonephritis, remain an important task for both modern nephrology and medicine in general. The aim of our work is to study the relationship between polymorphic variants of chemokine genes (+1931А/Т ССL4, A/G CXCL11 (rs4512021), -403A/G CCL5, C/G CCL2 (rs2857657), -801G/A CXCL12) and the features of clinical manifestations of chronic glomerulonephritis, namely with various clinical forms of the disease.

Conclusion

Thus, within the framework of the present work, the study of the associations of chemokines polymorphic genetic markers with the features of clinical manifestation of chronic glomerulonephritis was carried out. It was established, that the allele-801 A CXCL12 (OR = 1.85) could be considered as a marker for the development of hematuric form in patients with chronic glomerulonephritis.

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