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Angiotensin-converting enzyme gene polymorphism in North-west Indian children with posterior urethral valves

Kannan Laksmi Narasimhan1, Madhu Khullar, Balpinder Kaur

  • 1Department of Pediatric Surgery, Post Graduate Institute of Medical Education and Research, Chandigarh UT, 160012, India.

Journal of Pediatric Urology
|October 25, 2008
PubMed

Insights

The D allele of the angiotensin-converting enzyme (ACE) gene is linked to increased renal scarring in children with posterior urethral valves (PUV). This genetic factor, along with urinary tract infections, contributes to kidney damage progression.

Area of Science:

  • Genetics and Urology
  • Pediatric Nephrology

Background:

  • Posterior urethral valves (PUV) are a common cause of bladder outlet obstruction in male infants.
  • Renal scarring is a significant complication of PUV, potentially leading to chronic kidney disease.
  • The role of genetic factors, such as angiotensin-converting enzyme (ACE) gene polymorphism, in PUV outcomes is not fully understood.

Purpose of the Study:

  • To investigate the association between ACE gene insertion/deletion (I/D) polymorphism and other risk factors with renal scarring in patients with PUV.
  • To determine if specific ACE genotypes influence the development or progression of renal damage in PUV patients.

Main Methods:

  • A cohort of 40 male patients treated for PUV was retrospectively analyzed.
  • Patients were classified into groups based on the presence (n=28) or absence (n=12) of renal scars, confirmed by dimercato-succinic acid scans.
  • ACE I/D polymorphism was genotyped using polymerase chain reaction, comparing PUV patients with 100 healthy controls.

Main Results:

  • The D allele of the ACE gene was found in significantly higher frequency in PUV patients with renal scars (p=0.04).
  • Multivariate analysis indicated that the D allele conferred a 4.6-fold increased risk of renal scar formation (OR 4.6, p=0.04).
  • Breakthrough urinary tract infections (OR 7.5, p=0.006) and higher follow-up serum creatinine levels (OR 0.6, p=0.03) were also significantly correlated with renal scarring. Glomerular filtration rate (GFR) was significantly lower in patients with ID/DD genotypes compared to II genotype.

Conclusions:

  • The D allele of the ACE gene is associated with an increased risk and progression of renal scarring in patients with PUV.
  • Genetic predisposition, alongside factors like urinary tract infections, plays a role in the renal outcomes of PUV.
  • These findings suggest potential genetic screening or targeted interventions for PUV patients carrying the D allele.
Abstract

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