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白细胞介素8基因多态性与家族性膀胱输尿管反流无关联。

Lack of association of IL8 gene polymorphisms with familial vesico-ureteral reflux.

作者信息

Kuroda Seika, Puri Prem

机构信息

The Children's Research Centre, Our Lady's Children's Hospital, Crumlin, Dublin 12, Ireland.

出版信息

Pediatr Surg Int. 2007 May;23(5):441-5. doi: 10.1007/s00383-006-1857-7.

Abstract

Vesico-ureteral reflux (VUR) is the most common inherited disorder of the lower urinary tract. Children with VUR are at risk for ongoing renal damage with subsequent infections. IL8 is an important inflammatory mediator which can be produced by epithelial cells of the renal tract in response to a variety of inflammatory stimuli. High serum concentrations of IL-8 have been reported in patients with chronic renal failure. Elevated IL-8 levels have been reported in the urine of patients with VUR and renal parenchymal scarring (RPS). More recently it was reported that urine IL-8 levels remain elevated in infants with VUR even in the absence of a urinary tract infection (UTI). Increased IL-8 expression has been shown to be associated with polymorphism at position -251 (rs4073) of the IL-8 promoter. The aim of this study was to examine the association of IL-8 gene polymorphism with familial VUR in a cohort of 219 siblings from 109 families affected with VUR, the largest such cohort tested to date. RPS was assessed using dimercaptosuccinic acid scintigraphy. Genotyping was performed in 219 siblings with VUR (157 without RPS, 62 with RPS) and 292 controls for the position -251 of IL-8 gene by polymerase chain reaction with tetra primers and gel analysis. Genotype was compared using the chi square test. Statistical significance was taken as a value of P < 0.05. There were no significant differences in IL-8 -251 genotype frequency between VUR patients and controls. Similarly, gender, severity of VUR and renal parenchymal scarring had no effect on IL-8 -251 genotype frequency. Although IL-8 urinary levels have been reported to be elevated in VUR, our data indicate that IL-8 gene is not involved in the pathogenesis of familial VUR or reflux nephropathy.

摘要

膀胱输尿管反流(VUR)是下尿路最常见的遗传性疾病。患有VUR的儿童有持续肾脏损害及后续感染的风险。白细胞介素8(IL8)是一种重要的炎症介质,可由尿路的上皮细胞在受到多种炎症刺激时产生。慢性肾衰竭患者中已报道血清IL-8浓度较高。VUR和肾实质瘢痕形成(RPS)患者的尿液中IL-8水平也有升高的报道。最近有报道称,即使在没有尿路感染(UTI)的情况下,VUR婴儿的尿液IL-8水平仍会升高。已显示IL-8表达增加与IL-8启动子-251位(rs4073)的多态性相关。本研究的目的是在一个由109个受VUR影响的家庭中的219名兄弟姐妹组成的队列中检查IL-8基因多态性与家族性VUR的关联,这是迄今为止测试的最大此类队列。使用二巯基丁二酸闪烁扫描评估RPS。通过四引物聚合酶链反应和凝胶分析对219名患有VUR的兄弟姐妹(157名无RPS,62名有RPS)和292名对照进行IL-8基因-251位的基因分型。使用卡方检验比较基因型。统计学显著性以P < 0.05为标准。VUR患者和对照之间的IL-8 -251基因型频率没有显著差异。同样,性别、VUR严重程度和肾实质瘢痕形成对IL-8 -251基因型频率没有影响。虽然已有报道称VUR患者尿液中IL-8水平升高,但我们的数据表明IL-8基因不参与家族性VUR或反流性肾病的发病机制。

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