The Association of Cytokine Gene Polymorphism With Reflux Nephropathy
abstract
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Access this abstract now Full Text Available for ClinicalKey SubscribersObjective: To identify genetic risk factors for the progression of vesicoureteral reflux (VUR) to reflux nephropathy, we examined polymorphisms of multiple cytokine genes among VUR patients with or without renal scarring.
Methods: A total of 238 VUR patients aged between 1 and 18 years with (n = 113) or without renal scarring (n = 125) were included. The presence of renal scarring was demonstrated by renal parenchymal examination using Technetium-99m dimercaptosuccinate scintigraphy. Sera of the patients were examined for tumor necrosis factor-alpha (TNF-α, −308), transforming growth factor-beta1 (TGF-β1, +869, +915), interleukin-6 (IL-6, −174), interleukin-10 (IL-10, −1082, −819, −592) and interferon-gamma (IFN-γ, +874) gene polymorphisms using the polymerase chain reaction sequence-specific primer method.
Results: Among patients with renal scarring, frequencies for the T/T G/C and C/C G/C genotypes of TGF-β1 gene (p = 0.003), GCC/GCC genotype of IL-10 gene (p = 0.015), GC phenotype of IL-6 gene (p = 0.001) and T/T genotype of IFN-γ gene (p = 0.001) were higher compared to patients without renal scarring. Regarding the TNF-α gene, among patients with low grade VUR only, the G/G genotype was associated with an increased risk.
Conclusions: Certain genotypes of cytokine gene polymorphisms seem to be associated with an increased or decreased susceptibility to reflux nephropathy, which may explain why only a proportion of VUR patients progress to reflux nephropathy. This information may aid in prediction of prognosis and implementing more aggressive management strategies at earlier stages. Further immunogenetic studies may identify novel targets for the management and prevention of the condition.
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The Association of Cytokine Gene Polymorphism With Reflux Nephropathy
J Pediatr Urol 2013 Oct 01;9(5)653-658, K Fidan, S Gonen, O SoylemezogluFrom MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
This report presents an important and evolving perspective into reflux and the genetics of reflux. While much investigation to identify the genetic basis has occurred, no identification of a specific responsible gene or group of genes has been made. The critical element of reflux, however, is renal injury, and this paper addresses the possibility that the susceptibility to renal scarring may be inherited and based, in part, on patterns of inflammatory cytokines which determine the body’s response to infection.
The authors compared expression patterns of polymorphisms of important cytokines—such as TGF-ß1, interleukins-6 and -10, interferon gamma, and TNF-α—in children with and without renal scarring associated with reflux. They found clear differences in the prevalence of various polymorphisms of these cytokines, in which high levels of expression may be risk-enhancing or protective. No one cytokine is the key factor, of course, but these data suggest that a risk profile for individual patients might be developed based on a panel of cytokine polymorphisms. And this sort of risk profile might be very useful clinically to define which patients to investigate for reflux in the setting of a urinary tract infection or which patients to be more aggressive with in terms of treatment.
Other investigations have shown some risk factors for reflux-related scarring, including elements of the renin–angiotensin system.1,2,3 Others have examined the genetic basis of the susceptibility to acute pyelonephritis, which likely determines later scarring.4
The long-standing focus on the gene for reflux may have less value than identification of the mediators of renal injury associated with reflux, and this report offers valuable insight into a new, and probably more effective, strategy.
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