Vascular endothelial growth factor gene polymorphism is associated with calcium oxalate stone disease

Urol Res. 2003 Jul;31(3):218-22. doi: 10.1007/s00240-003-0325-2. Epub 2003 Apr 29.

Abstract

Growth factor-related genes regulate cell growth, differentiation and apoptosis in the kidney in response to cellular injury. One of the theories of stone formation is that cellular injury, and thus growth factors, play a role. We therefore investigated the association between growth factor genes and calcium oxalate stone disease. The most frequently seen polymorphism of the vascular endothelial growth factor (VEGF) gene is Bst U I C/T, which is located upstream at the -460th nucleotide. Other growth factor-related gene polymorphisms include the cytochrome P450c17alpha enzyme (CYP17) gene MspA I C/T polymorphism at the 5'-UTR promoter region, the epidermal growth factor receptor (EGFR) gene Bsr I polymorphism (A to T) at position 2,073, and the insulin-like growth factor-2 (IGF-2) gene Apa I A/G at exon 9. All four polymorphisms were used as genetic markers in this study in the search for an association between stone disease and growth factor related genes. A normal control group of 230 healthy people, and 230 patients with calcium oxalate stone, were examined. The polymorphism was seen following polymerase chain reaction based restriction analysis. The result revealed a significant difference between normal individuals and stone patients (P=0.0003, Fisher's exact test) in the distribution of the VEGF gene polymorphism as well as an odds ratio of 1.30 (95% confidence interval=0.993-1.715) per copy of the "T" allele. Whereas, the IGF-2, EGFR and CYP17 gene polymorphisms did not reveal a significant association with stone disease. We conclude that the VEGF gene Bst U I polymorphism is a suitable genetic marker of urolithiasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Base Sequence
  • Calcium Oxalate / metabolism*
  • Case-Control Studies
  • ErbB Receptors / genetics
  • Female
  • Humans
  • Insulin-Like Growth Factor II / genetics
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Polymerase Chain Reaction
  • Polymorphism, Genetic*
  • Steroid 17-alpha-Hydroxylase / genetics
  • Urinary Calculi / genetics*
  • Urinary Calculi / metabolism*
  • Vascular Endothelial Growth Factor A / genetics*

Substances

  • Vascular Endothelial Growth Factor A
  • Calcium Oxalate
  • Insulin-Like Growth Factor II
  • Steroid 17-alpha-Hydroxylase
  • ErbB Receptors