49 Mutation Screening in Patients with Vesico‐Ureteric Reflux

Abstract

Objectives Primary vesico‐ureteric reflux (VUR) is a very common anomaly of urogenital tract which makes affected children susceptible to repeated, severe urinary tract infections and possible subsequent permanent damage to the kidney function. The reflux is of genetic origin in most children but no candidate genes have been identified as yet. Studies on knock‐out mice with VUR phenotype have put forward the uroplakin genes (UPK1a, UPK1b, UPK2 UPK3) and the AGTR2 (angiotensin II type 2 receptor) gene as candidate genes for reflux in humans. Also, a recent genome wide linkage study detected several loci with significant LOD scores linked to VUR which included a locus for the uroplakin 1b gene. This study reports the results from screening of the coding regions of genes AGTR2, UPK1b and UPK3 in patients with primary vesico‐ureteric reflux.Design and methods The sample of 85 patients diagnosed with VUR was included in the study. Sequence variation screening in coding regions of the UPK1B gene was performed with the heteroduplex analysis followed by sequencing.Results No sequence variations were found in the coding exon 3 of the gene AGTR2 and only polymorphisms were present in the coding region of the gene UPK3. A sequence variation changing asparagin to aspartatic acid at the codon 137 (N137D) in exon 5 of the UPK1b gene was detected in 4.7% of patients with VUR and in 0.83% of controls (OR = 5.87, 95% CI 1.54–22.33, P = 0.017).Conclusions These results suggest that in our sample of patients the AGTR2 gene is not involved in the pathogenesis of reflux, they exclude the UPK3 gene as a candidate gene for VUR but they also associate the UPK1b gene with primary vesico‐ureteric reflux.