Functional polymorphisms in transforming growth factor-beta-1 (TGF -1) and vascular endothelial growth factor (VEGF) genes modify risk of renal parenchymal scarring following childhood urinary tract infection

Hussein, Almontaser; Askar, Eman; Elsaeid, Moustafa M.; Schaefer, Franz

doi:10.1093/ndt/gfp532

Cited by 43 publications

(39 citation statements)

References 42 publications

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“…Although we have not analyzed genetic susceptibility as the risk factor for ASL and USF several reports demonstrated the role of genetic susceptibilities as clinical determinants explain only a portion of individual risk [25]. Meta-analysis by Zaffanello et al revealed association between renal scarring formation after UTI and angiotensin enzyme insertion/deletion polymorphism or transforming growth factor-beta 1 c.509 T>C polymorphism [3,9,25].…”

Section: Discussionmentioning

confidence: 89%

The impact of therapeutic delay time on acute scintigraphic lesion and ultimate scar formation in children with first febrile UTI

Kim

Park

et al. 2011

Eur J Pediatr

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We assessed the role of therapeutic delay time (TDT) in acute renal cortical scintigraphic lesion (ASL) and ultimate scar formation (USF) in children with first febrile UTI and whether it is affected by the presence of vesico-ureteral reflux (VUR). 230 children, 90 girls and 140 boys with first febrile UTI were included. Radiologic (USG, DMSA, and VCUG), clinical (age, gender, peak fever, therapeutic delay time) and laboratory (CBC with differential count, ANC (absolute neutrophil count), BUN, Creatinine, urine analysis, gram stain, culture, CRP and ESR) variables were analysed. DMSA was performed within 5 days and after six months. VCUG was performed after acute phase of UTI. The differences in TDT according to the presence of ASL, USF and VUR were assessed. And the correlation between ASL or USF with the duration of TDT was assessed. Of 230 patients enrolled, 142 patients had refluxing UTI and 88 patients had non-refluxing UTI. TDT was the risk factor associated with ASL and USF along with presence of VUR. TDT was longer in ASL positive group compared with the ASL negative group. Also USF group showed longer TDT compared with those without USF in both refluxing UTI and non refluxing UTI. The TDT was significantly shorter in USF group with the presence of VUR. Positive linear association was noted between prevalence of ASL and USF and duration of TDT. In conclusion, the impact of UTI on formation of USF may be enhanced by the presence of VUR with shorter duration of TDT.

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Section: Discussionmentioning

confidence: 89%

The impact of therapeutic delay time on acute scintigraphic lesion and ultimate scar formation in children with first febrile UTI

Kim

Park

et al. 2011

Eur J Pediatr

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“…Genotype-phenotype analyses suggest that the C allele VEGF þ405G>C is associated with decreased promoter activity and decreased expression of VEGF, as the C allele reduces binding of the transcription factor, MZF1, which then subsequently reduces gene expression (72)(73)(74). Hence, the C allele VEGF þ405G>C may confer a survival advantage by reducing a tumor's ability to stimulate angiogenesis.…”

Section: Discussionmentioning

confidence: 99%

Vascular Endothelial Growth Factor Pathway Polymorphisms as Prognostic and Pharmacogenetic Factors in Cancer: A Systematic Review and Meta-analysis

Eng

Azad

Habbous

et al. 2012

Clinical Cancer Research

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Angiogenesis is an important host process that interacts with cancer cells to promote growth, invasion, and metastasis. Numerous therapeutic agents targeting the VEGF pathway have been developed. Host variability in VEGF pathway can influence angiogenesis-dependent signaling, altering sensitivity to antiangiogenic drugs and prognosis. A systematic review and meta-analysis was conducted (May 1990–July 2011). Eligible studies involved cancer patients and compared polymorphisms in the VEGF pathway [VEGF and molecules directly interacting with VEGF: KDR, FLT1, FGF, FGF2, FGFR, NRP1, endostatin (encoded by COL18A1)], and reported one of the following outcomes: overall survival, progression-free survival, time to recurrence, disease-free survival, response rate, or drug toxicity. We identified 48 cancer studies assessing prognosis and 12 cancer studies exploring pharmacogenetics of anti-VEGF therapy across various VEGF pathway polymorphisms. There was marked inter- and intradisease site heterogeneity in the effect of polymorphisms on both outcome and response to therapy. Meta-analyses of 5 VEGF polymorphisms (+936C>T, −460T>C, +405G>C, −1154G>A, and −2578C>A) identified a significant prognostic relationship: VEGF +405G>C variants showed a highly statistically significant improvement in overall survival [HR, 0.74; 95% confidence interval, 0.60–0.91; P = 0.004]. Variants (heterozygotes and/or homozygotes) of VEGF +405G>C were significantly associated with improved survival in a meta-analysis of multiple cancer sites. Clin Cancer Res; 18(17); 4526–37. ©2012 AACR.

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“…Some studies questioned the significance of ACE gene polymorphism as an independent risk factor for the development and progression of RN (Dudley et al, 2002;Pardo et al, 2003). An association between TGF-1 gene polymorphism and the risk of renal scarring in patients with vesicoureteral reflux was also disclosed Kowalewska-Pietrzak et al (2008), whereas Hussein et al (2010) demonstrated an association between vascular endothelium growth factor (VEGF) gene polymorphism and the risk of the development of RN.…”

Section: Reflux Nephropathymentioning

confidence: 99%

“…An association between polymorphism of angiotensin-converting enzyme gene and renal scarring was demonstrated (Haszon et al, 2002;Hohenfellner et al, 1999;Ohtomo et al, 2001;Ozen et al, 1999;Pardo et al, 2003). Similarly, polymorphism of transforming growth factor gene (Kowalewska-Pietrzak et al, 2008;Hussein et al, 2010) and polymorphism of vascular endothelium growth factor gene (Hussein et al, 2010) had impact on severity of renal scarring. Post-inflammatory nephropathy may be classified into reflux nephropathy due to vesicoureteral reflux and obstructive nephropathy due to urinary tract obstruction (Marra et al, 2004;Orikasa et al, 1995;Smellie et al, 1981).…”

Section: Urinary Tract Infections 310mentioning

confidence: 99%

Post-Inflammatory Nephropathy

Bieniaś¹,

Zajączkowska²,

Borzęcka³

et al. 2011

Urinary Tract Infections

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Functional polymorphisms in transforming growth factor-beta-1 (TGF -1) and vascular endothelial growth factor (VEGF) genes modify risk of renal parenchymal scarring following childhood urinary tract infection

Abstract: Activating variants in the TGFbeta-1 and VEGF gene promoters are associated with post-UTI renal scar formation in children. The TGFbeta-1 509T allele predicts renal scarring independent of VUR.

Cited by 43 publications

References 42 publications

The impact of therapeutic delay time on acute scintigraphic lesion and ultimate scar formation in children with first febrile UTI

The impact of therapeutic delay time on acute scintigraphic lesion and ultimate scar formation in children with first febrile UTI

Vascular Endothelial Growth Factor Pathway Polymorphisms as Prognostic and Pharmacogenetic Factors in Cancer: A Systematic Review and Meta-analysis

Post-Inflammatory Nephropathy

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