PDF(Pubmed)
Abstract：
BACKGROUND: Febrile urinary tract infections (UTIs) are among the most severe bacterial infections in infants, in which a subset of patients develops complications. Identifying infants at risk of recurrent infections or kidney damage based on clinical signs is challenging. Previous observations suggest that genetic factors influence UTI outcomes and could serve as predictors of disease severity. In this study, we conducted a nationwide survey of infant genotypes to develop a strategy for infection management based on individual genetic risk. Our aims were to identify genetic susceptibility variants for renal scarring (RS) and genetic host factors predisposing to dilating vesicoureteral reflux (VUR) and recurrent UTIs.
METHODS: To assess genetic susceptibility, we collected and analyzed DNA from blood using exome genotyping. Disease-associated genetic variants were identified through bioinformatics analysis, including allelic frequency tests and odds ratio calculations. Kidney involvement was defined using dimercaptosuccinic acid (DMSA) scintigraphy.
RESULTS: In this investigation, a cohort comprising 1087 infants presenting with their first episode of febrile UTI was included. Among this cohort, a subset of 137 infants who underwent DMSA scanning was subjected to gene association analysis. Remarkable genetic distinctions were observed between patients with RS and those exhibiting resolved kidney involvement. Notably, the genetic signature indicative of renal scarring prominently featured mitochondrial genes.
CONCLUSIONS: In this nationwide study of genetic susceptibility to RS after febrile UTIs in infancy, we identified a profile dominated by mitochondrial polymorphisms. This profile can serve as a predictor of future complications, including RS and recurrent UTIs.
METHODS: To assess genetic susceptibility, we collected and analyzed DNA from blood using exome genotyping. Disease-associated genetic variants were identified through bioinformatics analysis, including allelic frequency tests and odds ratio calculations. Kidney involvement was defined using dimercaptosuccinic acid (DMSA) scintigraphy.
RESULTS: In this investigation, a cohort comprising 1087 infants presenting with their first episode of febrile UTI was included. Among this cohort, a subset of 137 infants who underwent DMSA scanning was subjected to gene association analysis. Remarkable genetic distinctions were observed between patients with RS and those exhibiting resolved kidney involvement. Notably, the genetic signature indicative of renal scarring prominently featured mitochondrial genes.
CONCLUSIONS: In this nationwide study of genetic susceptibility to RS after febrile UTIs in infancy, we identified a profile dominated by mitochondrial polymorphisms. This profile can serve as a predictor of future complications, including RS and recurrent UTIs.
摘要：
背景：发热性尿路感染（UTI）是婴儿中最严重的细菌感染，其中一部分患者出现并发症。根据临床症状确定有反复感染或肾损害风险的婴儿是具有挑战性的。先前的观察表明，遗传因素会影响UTI的结果，并可以作为疾病严重程度的预测因子。在这项研究中,我们在全国范围内对婴儿基因型进行了调查,以制定基于个体遗传风险的感染管理策略.我们的目的是确定肾脏瘢痕形成（RS）的遗传易感性变异和易感扩张膀胱输尿管反流（VUR）和复发性UTI的遗传宿主因素。
方法：为了评估遗传易感性，我们使用外显子组基因分型从血液中收集和分析DNA.通过生物信息学分析鉴定了疾病相关的遗传变异，包括等位基因频率测试和比值比计算。使用二巯基琥珀酸（DMSA）闪烁显像术定义肾脏受累。
结果：在这项调查中，纳入了一个队列,该队列包括1087例首次出现高热UTI的婴儿.在这个群体中，对137例接受DMSA扫描的婴儿进行了基因关联分析.在RS患者和表现出肾脏受累的患者之间观察到了显着的遗传差异。值得注意的是,表明肾脏瘢痕形成的遗传特征是线粒体基因。
结论：在这项关于婴儿期高热UTI后RS遗传易感性的全国性研究中，我们确定了一个以线粒体多态性为主的谱。这个轮廓可以作为未来并发症的预测指标，包括RS和复发性UTI。
方法：为了评估遗传易感性，我们使用外显子组基因分型从血液中收集和分析DNA.通过生物信息学分析鉴定了疾病相关的遗传变异，包括等位基因频率测试和比值比计算。使用二巯基琥珀酸（DMSA）闪烁显像术定义肾脏受累。
结果：在这项调查中，纳入了一个队列,该队列包括1087例首次出现高热UTI的婴儿.在这个群体中，对137例接受DMSA扫描的婴儿进行了基因关联分析.在RS患者和表现出肾脏受累的患者之间观察到了显着的遗传差异。值得注意的是,表明肾脏瘢痕形成的遗传特征是线粒体基因。
结论：在这项关于婴儿期高热UTI后RS遗传易感性的全国性研究中，我们确定了一个以线粒体多态性为主的谱。这个轮廓可以作为未来并发症的预测指标，包括RS和复发性UTI。
