Vesicoureteric reflux in the UK – Establishing a DNA collection from affected families – second year report

A Stewart, A Gullett

The Institute of Human Genetics, International Centre for Life, Newcastle upon Tyne

Problem: Vesicoureteric Reflux (VUR) is the abnormal retrograde flow of urine from the bladder to the ureter and possibly to the kidney. It results from an inadequate length of submucosal ureteric tunnel, and can be the result of a congenital (present at birth) abnormality or it may be acquired. Reflux nephropathy (RN)is the disease associated with VUR and can occur if infected urine refluxes from the bladder into the kidneys, resulting in damage to the renal tissue, (focal defects/scarring). Primary VUR occurs in 1% of young children and their first-degree relatives have a 20-50% increased risk compared to the general population. Importantly, RN causes 10% of end-stage renal failure in the UK.

Purpose: The genetic bases are unclear but it was estimated that between 1& 4 major loci might be established by studying leukocyte DNA from 300 affected sibling-pairs and their parents. The resulting resource will allow the mapping of the major genetic loci and will assist in establishing more simplified diagnostic tests as well as defining the genetic basis of VUR.

Design: Funding had already been provided by The Wellcome Trust to include salaries for two research assistants for three years. Samples are collected from families where there are affected sibling pairs, i.e. where there is at least one child with primary VUR and/or reflux nephropathy (RN) plus another child (or other children) with either VUR or RN or both (VUR & RN).

Findings/Achievements: In the first two years, the UK VUR DNA & Database collection has achieved many of it aims. In association with the British Association of Paediatric Nephrology (BAPN), we have successfully established a large network of contacts throughout the UK, obtaining both R&D and ethical approval at all our multi-regional centres with honorary contracts being issued at each prior to sample collection (12 nephrology centres, 25 paediatric units and 2 genetics centres). To date, we have collected 110 families who have two (or more) affected siblings. A project-specific database has been developed to store significant renal information about the families involved and a dedicated website (www.vur.org.uk) informs potential investigators and families about VUR and will document the future use of the DNA Bank. The National Kidney Research Fund through whom the DNA Development Group has been established, are responsible for the promotion of the study and will act as independent assessors of requests to access the resource once the project is complete. (NB Numbers in red will have increased significantly by June 2005)

Conclusion: Based on this second year progress report, the collection of 300 families is on-course and a firm multidisciplinary infrastructure has been established.

Relevance: This project will establish a VUR DNA Bank and Database, providing a strong foundation for investigators interested in defining the genetic basis of VUR and other urinary tract malformations, which may lead to a simple genetic test for identifying VUR and increase our understanding of urinary tract development.