A genome scan in affected sib-pairs with familial vesicoureteral reflux identifies a locus on chromosome 5

Abstract

The basis for vesicoureteral reflux (VUR) is considered to be primarily genetic, with a 30-50% incidence of VUR in first-degree relatives of patients. The search for the causative gene or genes has been elusive, likely because of VUR being genetically heterogeneous with complex inheritance patterns. In this study, a genome-wide analysis of VUR with high-density single nucleotide polymorphisms was conducted with the aim of identifying susceptibility loci for VUR in 98 families with two or more affected children. Using the affected sib-pair method of analysis in 150 sib-pairs, we identified a genome-wide statistically significant linkage peak with an LOD score greater than 4 on chromosome 5 and two linkage peaks with LOD scores greater than 3.6 on chromosomes 13 and 18 were identified in these 98 families. These results suggested that multiple genes are likely to contribute to the formation of VUR phenotype. Further mapping of these linkage peaks may help identify the causative genes.

Vesico-ureteric reflux: using mouse models to understand a common congenital urinary tract defect

“…Genetic studies of families and patients with VUR have revealed that the condition is extremely genetically heterogeneous [39][40][41][42]. Four major strategies have been used to explore the genetic basis of VUR in humans: candidate gene approaches [43][44][45], studies of patients with VUR and chromosomal abnormalities [46][47][48][49], studies of patients with rare syndromes that have VUR in addition to other congenital abnormalities [50][51][52][53][54], and whole-genome mapping [39][40][41][42][55][56][57][58]. From these studies, a number of different genes and loci have been associated with VUR, demonstrating that it is genetically complex (Fig.…”

The significance of Pax2 expression in the ureter epithelium of children with vesicoureteric reflux

“…Defects in these genes in mice lead to kidney and urinary tract anomalies, including renal agenesis, duplex systems, obstruction, hydronephrosis, and hydroureter [4][5][6][7][8][9]. However, although alterations of these genes have been observed in humans, little evidence supports the association of these genes with VUR [10][11][12][13].…”

Costs and Consequences of Universal Sibling Screening for Vesicoureteral Reflux: Decision Analysis

“…1 Despite a reported prevalence of VUR of ~1% in the general pediatric population, the prevalence of VUR has been shown to be 27% among siblings of patients with VUR. The prevalence of VUR among siblings decreases with age but is not significantly associated with sibling or proband gender.…”