title: Role of TGF-beta1 in renal parenchymal scarring following childhood urinary tract infection.
abstract: BACKGROUND
  Significant variability exists in the outcome of renal parenchymal inflammation following urinary tract infection (UTI) in childhood as some children experience renal parenchymal scarring (RPS) while others do not scar. Since TGF-beta1 is pro-fibrotic, we examined the role of this cytokine in RPS following UTI.
  
  
  METHODS
  Five polymorphisms of the TGF-beta1 gene were investigated as well as the relationship between these polymorphisms and TGF-beta1 production by peripheral blood mononuclear cells (PBMC) in vitro. DNA was isolated from 91 children shown to have developed RPS, 43 children with no evidence of scarring (NS) following UTI, and 171 healthy controls. Genotyping was performed by restriction fragment length polymorphism (RFLP). PBMC were isolated from a subgroup of 24 patients from the total population. Cells were stimulated with LPS + PMA + PHA and then TGF-beta1 production was determined by ELISA.
  
  
  RESULTS
  Comparing the NS with the RPS group, there was an increase in the -800 GA genotypes (18.6 vs. 7.4%, P=0.05; chi2) and the Leu10-->Pro CT (62.8 vs. 41.5%, P=0.021), and a decrease in the -509 TT genotype (0.0 vs. 8.5%, P=0.049). PBMC TGF-beta1 production was higher in those patients with the -800 GG compared to those with a GA genotype stimulation index [stimulated/unstimulated TGF-beta1 levels were 1.54 interquartile range (IQR) 1.42 to 1.75 vs. 1.19, IQR 0.94 to 1.51, P=0.031].
  
  
  CONCLUSIONS
  There is an association between the TGF-beta1 -800 GA, -509 TT and Leu10-->Pro CT genotypes and the presence or absence of RPS. The low TGF-beta1 producer status of the -800 GA genotype may protect against the development of a pro-fibrotic pathology.
authors.affiliation: Renal Research Laboratories, Manchester Institute of Nephrology and Transplantation, Manchester Royal Infirmary, Manchester, England, United Kingdom. s.a.cotton@man.ac.uk
authors.forename: Shirley A
authors.initials: SA
authors.lastname: Cotton
authors.forename: Rasheed A
authors.initials: RA
authors.lastname: Gbadegesin
authors.forename: Shelley
authors.initials: S
authors.lastname: Williams
authors.forename: Paul E C
authors.initials: PE
authors.lastname: Brenchley
authors.forename: Nicholas J A
authors.initials: NJ
authors.lastname: Webb
mesh_terms: D002648:Child; D002675:Child, Preschool; D002921:Cicatrix / Q000276:immunology / Q000473:pathology; D005260:Female; D005355:Fibrosis; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D066298:In Vitro Techniques; D007223:Infant; D007668:Kidney / Q000276:immunology / Q000473:pathology*; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D012150:Polymorphism, Restriction Fragment Length; D016212:Transforming Growth Factor beta / Q000235:genetics* / Q000276:immunology*; D053773:Transforming Growth Factor beta1; D014552:Urinary Tract Infections / Q000235:genetics* / Q000276:immunology* / Q000473:pathology
chemical_list: C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1