Abstract
Fractalkine (CX3CL1) is a chemokine that plays a significant role in inflammation, one of the pathophysiological processes underlying end-stage renal disease (ESRD). Genetic factors are significantly involved in cytokine expression and have been studied as potential risk factors for chronic kidney disease (CKD). Objectives: We aimed to elucidate the association of CX3CR1 gene polymorphisms rs3732378 and rs3732379 with the levels of CX3CL1, CX3CL1 receptor (CX3CR1), as well as C-reactive protein (CRP). Patients and methods: We enrolled 198 participants, including 106 patients with ESRD and 92 controls. Peripheral blood samples were collected from each patient for genetic (rs3732378 and rs3732379 polymorphisms) and immunoenzymatic (fractalkine, CX3CR1, CRP) tests. Results: CX3CR1 and CRP levels were higher in patients with ESRD than in controls (p < 0.05). Fractalkine levels were significantly higher in ESRD patients who were homozygous for the G allele of the rs3732378 polymorphism and for the C allele of the rs3732379 polymorphism than in homozygous controls. Moreover, carriers of these alleles among patients with ESRD had significantly higher CX3CR1 levels than controls. Conclusions: The G allele of the rs3732378 polymorphism and the C allele of the rs3732379 polymorphism of the CX3CR1 gene are associated with higher CX3CL1 and CX3CR1 levels. Our study suggests that CX3CR1 gene polymorphisms could be potentially involved in the pathogenesis of ESRD, but the study needs to be replicated in a larger population with a longitudinal follow-up study. Identification of genetic factors associated with inflammation in ESRD may contribute to the development of targeted gene therapies in the future.
Highlights
Chronic kidney disease (CKD) is a condition in which there is gradual reduction in the number of nephrons and loss of kidney function over time
The inclusion criteria for cases were as follows: estimated glomerular filtration rate (eGFR) category G5 according to the Kidney Disease: Improving Global Outcomes (KDIGO) classification, need for hemodialysis (ESRD at the onset of hemodialysis, i.e., eGFR < 15 mL/min/1.73 m2 ), and informed consent to participate in the study
The G allele was predominant in both groups, while the A allele was present in about 28% of the study group, which is consistent with the frequency of alleles for the rs3732378 polymorphism in the white population (Table 2)
Summary
Chronic kidney disease (CKD) is a condition in which there is gradual reduction in the number of nephrons and loss of kidney function over time. Improving Global Outcomes (KDIGO) [1], CKD is defined as structural or functional abnormalities of kidneys, present for at least three months, with important implications for health. The possible reasons for this include low awareness among clinicians about the need for nephroprotection in the treatment of other diseases, as well as the underestimated role of chronic inflammation as the main atherogenic factor [5]. Proinflammatory cytokines and their derivatives (i.e., chemokines) play a major role in the pathogenesis of inflammatory processes [6].
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