The association of cytokine gene polymorphism with reflux nephropathy |
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| Affiliation: | 1. Faculty of Medicine, Department of Pediatric Nephrology, Gazi University Hospital, Besevler, Ankara 06500, Turkey;2. Laboratory of Pediatric Nephrology, Gazi University Hospital, Ankara, Turkey;1. Pediatric Uronephrologic Center, The Queen Silvia Children''s Hospital, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden;2. The Children''s Memorial Health Institute, Warsaw, Poland;1. Department of Urology, University of Iowa Hospitals and Clinics, Iowa City, IA, USA;2. Department of Pediatrics, University of Iowa Hospitals and Clinics, Iowa City, IA, USA;1. Division of Pediatric Urology, Hospital for Sick Children, Toronto, Canada;2. Division of Pediatric Urology, Hospital Universitario San Ignacio, Pontificia Universidad Javeriana, Bogota, Colombia;3. Department of Paediatric Urology, Children''s Hospital of Eastern Ontario, Ottawa, Canada;4. Department of Pediatric Urology, Children''s Healthcare of Atlanta and Emory University School of Medicine, Atlanta GA, USA;5. Department of Pediatric Urology, Hasbro Children''s Hospital, Brown University, Providence RI, USA;1. Department of Pediatric Surgery, The Pediatric Uronephrologic Centre, The Queen Silvia Children''s Hospital, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden;2. Pediatric Clinical Physiology, The Pediatric Uronephrologic Centre, The Queen Silvia Children''s Hospital, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden;3. Pediatric Radiology, The Paediatric Uronephrologic Centre, The Queen Silvia Children''s Hospital, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden;1. Department of Pediatric Neurology, Fukuoka Children’s Hospital, Fukuoka, Japan;2. Department of Nephrology, Fukuoka Children’s Hospital, Fukuoka, Japan;3. Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan;1. Division of Urology, Hospital for Sick Children and Department of Surgery, University of Toronto, Ontario, Canada;2. Center for Computational Medicine, Hospital for Sick Children, Toronto, Ontario, Canada;3. Division of Pediatric Urology, UH Rainbow Babies and Children''s Hospital, Cleveland, OH, USA;4. Department of Pediatrics, Hospital for Sick Children, Toronto, Ontario, Canada |
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| Abstract: | ObjectiveTo 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.MethodsA 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.ResultsAmong 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.ConclusionsCertain 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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