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A genetic basis of susceptibility to acute pyelonephritis.

Lundstedt, Ann-Charlotte LU ; McCarthy, Shane; Gustafsson, Mattias LU ; Godaly, Gabriela LU ; Jodal, Ulf; Karpman, Diana LU ; Leijonhufvud, Irene LU ; Lindén, Carin; Martinell, Jeanette and Ragnarsdottir, Bryndis LU , et al. (2007) In PLoS ONE 2(9). p.10-825
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.

Methods and Findings



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... (More)
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.

Methods and Findings



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. (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
PLoS ONE
volume
2
issue
9
pages
10 - 825
publisher
Public Library of Science
external identifiers
  • wos:000207455500009
  • scopus:41049104005
ISSN
1932-6203
DOI
10.1371/journal.pone.0000825
language
English
LU publication?
yes
id
601a9784-a115-43e1-9a25-51d1b4e1a639 (old id 607964)
date added to LUP
2008-08-19 09:13:17
date last changed
2017-09-10 04:28:25
@article{601a9784-a115-43e1-9a25-51d1b4e1a639,
  abstract     = {Background<br/><br>
<br/><br>
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.<br/><br>
Methods and Findings<br/><br>
<br/><br>
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&lt;0.001 and p&lt;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&lt;0.0001) and two sequence variants were shown to impair transcription.<br/><br>
Conclusions<br/><br>
<br/><br>
The results identify a genetic innate immune deficiency, with a strong link to APN and renal scarring.},
  author       = {Lundstedt, Ann-Charlotte and McCarthy, Shane and Gustafsson, Mattias and Godaly, Gabriela and Jodal, Ulf and Karpman, Diana and Leijonhufvud, Irene and Lindén, Carin and Martinell, Jeanette and Ragnarsdottir, Bryndis and Samuelsson, Martin and Truedsson, Lennart and Andersson, Björn and Svanborg, Catharina},
  issn         = {1932-6203},
  language     = {eng},
  number       = {9},
  pages        = {10--825},
  publisher    = {Public Library of Science},
  series       = {PLoS ONE},
  title        = {A genetic basis of susceptibility to acute pyelonephritis.},
  url          = {http://dx.doi.org/10.1371/journal.pone.0000825},
  volume       = {2},
  year         = {2007},
}