title: A genetic basis of susceptibility to acute pyelonephritis.
abstract: BACKGROUND
  For unknown reasons, urinary tract infections (UTIs) are clustered in certain individuals. Here we propose a novel, genetically determined cause of susceptibility to acute pyelonephritis, which is the most severe form of UTI. The IL-8 receptor, CXCR1, was identified as a candidate gene when mIL-8Rh mutant mice developed acute pyelonephritis (APN) with severe tissue damage.
  
  
  RESULTS
  We have obtained CXCR1 sequences from two, highly selected APN prone patient groups, and detected three unique mutations and two known polymorphisms with a genotype frequency of 23% and 25% compared to 7% in controls (p<0.001 and p<0.0001, respectively). When reflux was excluded, 54% of the patients had CXCR1 sequence variants. The UTI prone children expressed less CXCR1 protein than the pediatric controls (p<0.0001) and two sequence variants were shown to impair transcription.
  
  
  CONCLUSIONS
  The results identify a genetic innate immune deficiency, with a strong link to APN and renal scarring.
authors.affiliation: Department of Microbiology, Immunology and Glycobiology, Institute of Laboratory Medicine, Lund University, Lund, Sweden.
authors.forename: Ann-Charlotte
authors.initials: AC
authors.lastname: Lundstedt
authors.forename: Shane
authors.initials: S
authors.lastname: McCarthy
authors.forename: Mattias C U
authors.initials: MC
authors.lastname: Gustafsson
authors.forename: Gabriela
authors.initials: G
authors.lastname: Godaly
authors.forename: Ulf
authors.initials: U
authors.lastname: Jodal
authors.forename: Diana
authors.initials: D
authors.lastname: Karpman
authors.forename: Irene
authors.initials: I
authors.lastname: Leijonhufvud
authors.forename: Carin
authors.initials: C
authors.lastname: Lindén
authors.forename: Jeanette
authors.initials: J
authors.lastname: Martinell
authors.forename: Bryndis
authors.initials: B
authors.lastname: Ragnarsdottir
authors.forename: Martin
authors.initials: M
authors.lastname: Samuelsson
authors.forename: Lennart
authors.initials: L
authors.lastname: Truedsson
authors.forename: Björn
authors.initials: B
authors.lastname: Andersson
authors.forename: Catharina
authors.initials: C
authors.lastname: Svanborg
mesh_terms: D000208:Acute Disease; D000818:Animals; D001483:Base Sequence; D016022:Case-Control Studies; D017931:DNA Primers; D024202:Electrophoretic Mobility Shift Assay; D020022:Genetic Predisposition to Disease; D006801:Humans; D051379:Mice; D008817:Mice, Mutant Strains; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D011704:Pyelonephritis / Q000235:genetics*; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000235:genetics; D023062:Receptors, Interleukin-8A / Q000235:genetics