The Molecular Genetics of Vesicoureteral Reflux

Project Description

Funding Children’s Medical & Research Foundation.
Principal Investigator Dr David Barton.
Researchers Dr Akihiro Yoneda, Ms Helena Kelly (PhD Student).
Duration March 1998 - Present.
Collaborators Mr Prem Puri, Our Lady’s Hospital for Sick Children; Dr Denis Shields, RCSI; Dr Cliona Molony, University of Pennsylvania.

Introduction

Vesicoureteral reflux (VUR), the retrograde flow of urine from the bladder into the ureter and kidney, is a common disorder, found in 1-2% of children.

This reverse flow of urine can cause kidney damage (reflux nephropathy) by itself, and the risk of damage is increased by the urinary tract infections to which affected children are susceptible.

VUR is the most common cause of end-stage renal failure and of severe hypertension in children. The anatomical basis of the disorder is a shortening of the segment of the ureter which runs through the submucosal layer of the bladder wall.

Reflux can be corrected by an endoscopic procedure involving injecting Teflon paste beneath the truncated ureter in the bladder wall (STING procedure), invented in the Children’s Research Centre in 1984.

Siblings of children with VUR are at greatly increased risk of being affected themselves, indicating that a genetic susceptibility factor (or factors) is involved.

We assembled a collection of 170 pairs of siblings affected with VUR and their parents. We are using this resource to search for the VUR susceptibility gene(s).

This analysis will map the VUR susceptibility gene(s), which will allow us to diagnose VUR in siblings of affected parents without the use of invasive testing, and will be the first step towards identifying this gene (or genes) and studying its function.

Publications

  1. Linkage Analysis of Candidate Genes in Families With Vesicoureteral Reflux. Kelly H, Barton D, Molony C and Puri P J Urol. (Epub ahead of print): 17 Aug. 2009 IMPACT FACTOR: 3.952
  2. The increased incidence of the RET p.Gly691Ser variant in French-Canadian vesicoureteric reflux patients is not replicated by a larger study in Ireland. Darlow JM, Molloy NH, Green AJ, Puri P and Barton DE Hum Mutat. 30 (5): 612-617, May 2009 IMPACT FACTOR: 7.033
  3. Familial Vesicoureteral Reflux-Is Screening Beneficial? Menezes M and Puri P., J Urol. (Epub ahead of print): 18 Aug. 2009 IMPACT FACTOR: 3.952
  4. A genome-wide scan for genes involved in primary vesicoureteric reflux. Kelly H, Molony CM, Darlow JM, Pirker ME, Yoneda A, Green AJ, Puri P and Barton DE J. Med Genet. (Epub ahead of print) 44 (11): 710-7, May 2009 IMPACT FACTOR: 5.713
  5. Association of transforming growth factor-beta1 gene polymorphism with familial vesicoureteral reflux. Kuroda S, Solari V and Puri P J Urol. 178: 1650-3, Oct 2007 IMPACT FACTOR: 3.952
  6. Lack of association of IL8 gene polymorphisms with familial vesico-ureteral reflux. Kuroda S and Puri P Pediatr Surg Int. 23 (5): 441-445, 2007 IMPACT FACTOR: 0.964
  7. Renal scarring in familial vesicoureteral reflux: is prevention possible? Pirker ME, Colhoun E and Puri P J Urol. 176: 1842-1846, 2006 IMPACT FACTOR: 3.952
  8. Familial Vesicoureteral Reflux: Influence of Sex on Prevalence and Expression. Pirker ME, Mohanan N, Colhoun E, Barton D, Green A and Puri P J. Urol 176: 1776-1780, 2006 IMPACT FACTOR: 3.952
  9. Uroplakin III is not a major candidate gene for primary vesicoureteral reflux. Kelly H, Ennis S, Yoneda A, Bermingham C, Shields DC, Molony C Green AJ, Puri P and Barton D Eur J Hum Genet 13: 500-502, 2005 IMPACT FACTOR: 3.952
  10. Angiotensin II type 2 receptor gene is not responsible for familial vesicoureteral reflux. Yoneda A, Cascio S, Green A, Barton DE and Puri P Urol. 168 (3): 1138-41, 2002