A genetic basis of susceptibility to acute pyelonephritis.
Author
Summary, in English
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.
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.
Department/s
Publishing year
2007
Language
English
Pages
10-825
Publication/Series
PLoS ONE
Volume
2
Issue
9
Full text
- Available as PDF - 419 kB
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Document type
Journal article
Publisher
Public Library of Science (PLoS)
Topic
- Microbiology in the medical area
Status
Published
Research group
- Clinical Microbiology, Malmö
- Pediatric Nephrology
ISBN/ISSN/Other
- ISSN: 1932-6203