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PLoS One. 2007 Sep 5;2(9):e825.

A genetic basis of susceptibility to acute pyelonephritis.

Author information

1
Department of Microbiology, Immunology and Glycobiology, Institute of Laboratory Medicine, Lund University, Lund, Sweden.

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 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.

PMID:
17786197
PMCID:
PMC1950574
DOI:
10.1371/journal.pone.0000825
[Indexed for MEDLINE]
Free PMC Article

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