Primary, nonsyndromic vesicoureteric reflux and its nephropathy is genetically heterogeneous, with a locus on chromosome 1

Am J Hum Genet. 2000 Apr;66(4):1420-5. doi: 10.1086/302864. Epub 2000 Mar 17.


Primary vesicoureteric reflux (VUR) affects 1%-2% of whites, and reflux nephropathy (RN) causes up to 15% of end-stage renal failure in children and adults. There is a 30-50-fold increased incidence of VUR in first-degree relatives of probands, compared with the general population. We report the results of the first genomewide search of VUR and RN; we studied seven European families whose members exhibit apparently dominant inheritance. We initially typed 387 polymorphic markers spaced, on average, at 10 cM throughout the genome; we used the GENEHUNTER program to provide parametric and nonparametric linkage analyses of affected individuals. The most positive locus spanned 20 cM on 1p13 between GATA176C01 and D1S1653 and had a nonparametric LOD score (NPL) of 5.76 (P=.0002) and a parametric LOD score of 3.16. Saturation with markers at 1-cM intervals increased the NPL to 5.94 (P=.00009). Hence, VUR maps to a locus on chromosome 1. There was evidence of genetic heterogeneity at the chromosome 1 locus, and 12 additional loci were identified genomewide, with P<.05. No significant linkage was found to 6p, where a renal and ureteric malformation locus has been reported, or to PAX2, mutations of which cause VUR in renal-coloboma syndrome. Our results support the hypothesis that VUR is a genetic disorder.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chromosome Mapping
  • Chromosomes, Human, Pair 1 / genetics*
  • Europe
  • Female
  • Genes, Dominant / genetics
  • Genetic Heterogeneity*
  • Genetic Markers / genetics
  • Genetic Predisposition to Disease / genetics
  • Genome, Human
  • Humans
  • Kidney Diseases / genetics*
  • Kidney Diseases / pathology
  • Lod Score
  • Male
  • Models, Genetic
  • Pedigree
  • Polymorphism, Genetic / genetics
  • Software
  • Statistics, Nonparametric
  • Syndrome
  • Vesico-Ureteral Reflux / genetics*
  • Vesico-Ureteral Reflux / pathology*


  • Genetic Markers