Protective locus against renal scarring on chromosome 11 in affected sib pairs with familial vesicoureteral reflux identified by single nucleotide polymorphism linkage analysis

Purpose: We identified the loci associated with renal scarring risk and protection in affected sib pairs with familial vesicoureteral reflux.

Materials and methods: A genome-wide analysis of vesicoureteral reflux with high density single nucleotide polymorphisms was conducted in 43 families with 2 or more affected children. A total of 43 probands and 58 affected siblings were included in the analysis. Genomic DNA was extracted from blood or saliva from all patients. All nuclear families had complete parental genotypes and all were Caucasian. Renal scarring was present in 23 of the 43 probands as detected by dimercapto-succinic acid imaging. easyLINKAGE software was used for the genome-wide linkage analysis. A LOD (logarithm [base 10] of odds) score of 3.3 or greater was considered significant evidence of linkage and a LOD score of 2.4 or greater but less than 3.3 was considered suggestive evidence of linkage.

Results: Using the affected sib pair method of analysis, a statistically significant linkage peak with a multipoint LOD score of 3.66 for patients without renal scarring was identified on chromosome 11 at 47.97 cM. For the scarring group a peak with a multipoint LOD score of 2.69 was identified on chromosome 17, which provides suggestive evidence of linkage.

Conclusions: Our results suggest that a locus on chromosome 11 is associated with protection against renal scarring in patients with vesicoureteral reflux. In addition, a new locus on chromosome 17 may be linked to renal scarring. Our results suggest that multiple genes contribute to the formation of the vesicoureteral reflux phenotype, with patients having a unique susceptibility to renal injury/damage.