The United Kingdom Vesicoureteric Reflux (VUR) DNA Collection
A collaboration between the Institute of Child Health, London and the Institute of Human Genetics, Newcastle upon Tyne
What is VUR and what are its consequences?
VUR is the retrograde passage of urine from the bladder into the upper urinary tract. The primary form is due to ectopic, lateral insertion of the ureter into the bladder via a shortened tunnel through the detrusor muscle. This leads to failure of valve-like closure during bladder filling and micturition. VUR affects young children and in 80% resolves by the age of ten. About a quarter of affected children have an associated nephropathy (reflux nephropathy also known as chronic pyelonephritis). In most this is secondary to scarring associated with ascending bacterial infection but in some the nephropathy is part of the developmental abnormality. Depending on the severity of the nephropathy, proteinuria, hypertension and renal failure may ensue.
The Familial aspects of VUR
VUR runs in families; up to 50% of siblings and offspring of affected individuals have the condition. About 1% of the population has VUR and this makes it one of the commonest inherited conditions. Despite this, very little is known about the underlying genetic abnormalities. We have identified a locus on chromosome 1 but have also shown that the condition is genetically heterogeneous (Feather et al, Am.J.Hum.Genet. 2000;66:1420-1425). The availability of such information would make feasible genetic screening to replace the invasive radiological investigations currently undertaken.
The UK VUR DNA Collection
With funding from the Wellcome Trust we have undertaken a collection of DNA from 189 UK index cases with VUR and their 219 affected siblings..The DNA samples are stored in the regional NHS diagnostic laboratory in Newcastle according to rigorous national guidelines. Multi-centre Research Ethics Committee (MREC) approval has been given for the study. With funding from the Medical Research Council we have undertaken a whole genome linkage and association study on these samples and those from an additional 131 sibling pairs collected in Slovenia with funding from the Wellcome Trust. Based on this DNA collection, an initial genome-wide analysis has been performed and the results published in the Journal of the American Society of Nephrology - Cordell HJ et al. 2010; 21: 113-123.
Kidney Research UK has acted as a facilitator in this project working with the primary research partners, the British Association for Paediatric Nephrology (BAPN) and other agreed collaborators to collectively form a VUR development group which assisted with the establishment and maintenance of the DNA collection.
Accessing the Collection
The collection is freely available to the wider research community (terms and conditions). Requests to use samples from the collection are considered by an oversight committee chaired by Dr John Bradley. Requests should be sent by email, as a Word document, to firstname.lastname@example.org. They should be no longer than one side of A4 and should cover the nature, rationale and technical aspects of the study, including the number of samples that will be analysed (from the collection and other sources) together with the appropriate power calculation. The application should also include two relevant citations, the source of funding for the study and a demonstration that the applicants have the technical expertise to perform the studies. A short lay description should also be included. It is anticipated that decisions will be made within a month of the request being made, and often more swiftly. Studies that involve collaboration with members of the VUR study group (for details see Cordell et al, J Am Soc Nephrol. 2010 Jan;21:113-23) are particularly welcome.