PloS one · 2007
A genetic basis of susceptibility to acute pyelonephritis.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Lundstedt Ann-Charlotte, McCarthy Shane, Gustafsson Mattias C U, Godaly Gabriela, Jodal Ulf, Karpman Diana, Leijonhufvud Irene, Lindén Carin, Martinell Jeanette, Ragnarsdottir Bryndis, Samuelsson Martin, Truedsson Lennart, Andersson Björn, Svanborg Catharina
Аннотация
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.
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.
Предметные рубрики MeSH
Acute DiseaseAnimalsBase SequenceCase-Control StudiesDNA PrimersElectrophoretic Mobility Shift AssayGenetic Predisposition to DiseaseHumansMiceMice, Mutant StrainsPolymerase Chain ReactionPolymorphism, Single NucleotidePyelonephritisRNA Processing, Post-TranscriptionalRNA, MessengerReceptors, Interleukin-8A