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

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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 P450c17α 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.

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Reference

  1. Biason A, Mantero F, Scaroni C, Simpson ER, Waterman MR (1991) Deletion within the CYP17 gene together with insertion of foreign DNA is the cause of combined complete 17 alpha-hydroxylase/17,20-lyase deficiency in an Italian patient. Mol Endocrinol 5: 2037

    CAS  PubMed  Google Scholar 

  2. Chen WC, Wu HC, Lin WC, Wu MC, Hsu CD, Tsai FJ (2001) The association of androgen- and estrogen-receptor gene polymorphisms with urolithiasis in men. BJU Int 88: 432

    Article  CAS  PubMed  Google Scholar 

  3. Cvetkovic D, Movsas B, Dicker AP, Hanlon AL, Greenberg RE, Chapman JD, Hanks GE, Tricoli JV (2001) Increased hypoxia correlates with increased expression of the angiogenesis marker vascular endothelial growth factor in human prostate cancer. Urology 57: 821

    Article  CAS  PubMed  Google Scholar 

  4. DeWater R, Noordermeer C, Houtsmuller AB, Nigg AL, Stijnen T, Schroder FH, Kok DJ (2000) Role of macrophages in nephrolithiasis in rats: an analysis of the renal interstitium. Am J Kidney Dis 36: 615

    CAS  PubMed  Google Scholar 

  5. Ferrara N, Houck KA, Jakeman LB, Winer J, Leung DW (1991) The vascular endothelial growth factor family of polypeptides. J Cell Biochem 47: 211

    CAS  PubMed  Google Scholar 

  6. Ferrer FA, Miller LJ, Andrawis RI, Kurtzman SH, Albertsen PC, Laudone VP, Kreutzer DL (1997) Vascular endothelial growth factor (VEGF) expression in human prostate cancer: in situ and in vitro expression of VEGF by human prostate cancer cells. J Urol 157: 2329

    CAS  PubMed  Google Scholar 

  7. Finlayson B, Reid F (1978) The expectation of free and fixed particles in urinary stone disease. Invest Urol 15: 442

    CAS  PubMed  Google Scholar 

  8. Gnanapragasam YJ, Mccahy PJ, Neal DE, Robon CN (2000) Insulin-like growth factor II and androgen receptor expression in the prostate. BJU Int 86: 731

    Article  CAS  PubMed  Google Scholar 

  9. Hackett RL, Shevock PN, Khan SR (1990) Cell injury associated calcium oxalate crystalluria. J Urol 144: 1535

    CAS  PubMed  Google Scholar 

  10. Habuchi T, Liqing Z, Suzuki T, Sasaki R, Tsuchiya N, Tachiki H, Shimoda N, Satoh S, Sato K, Kakehi Y, Kamoto T, Ogawa O, Kato T (2000) Increased risk of prostate cancer and benign prostatic hyperplasia associated with a CYP17 gene polymorphism with a gene dosage effect. Cancer Res 60: 5710

    CAS  PubMed  Google Scholar 

  11. Huang CS, Chern HD, Chang KJ, Cheng CW, Hsu SM, Shen CY (1999) Breast cancer risk associated with genotype polymorphism of the estrogen-metabolizing genes CYP17, CYP1A1, and COMT: a multigenic study on cancer susceptibility Cancer Res 59: 4870

    Google Scholar 

  12. Jackson MW, Bentel JM, Tilley WD (1997) Vascular endothelial growth factor (VEGF) expression in prostate cancer and benign prostatic hyperplasia. J Urol 157: 2040

    PubMed  Google Scholar 

  13. Joseph IB, Nelson JB, Denmeade SR, Isaacs JT (1997) Androgen regulate vascular endothelial growth factor content in normal and malignant prostatic tissue. Clin Cancer Res 3: 2507

    CAS  PubMed  Google Scholar 

  14. Kok DJ, Khan SR (1994) Calcium oxalate nephrolithiasis, a free or fixed particle disease. Kidney Int 46: 847

    CAS  PubMed  Google Scholar 

  15. Krepinsky J, Ingram AJ, Churchill DN (2000) Metabolic investigation of recurrent nephrolithiasis: compliance with recommendations. Urology 56: 915

    Article  CAS  PubMed  Google Scholar 

  16. Nishijima S, Sugaya K, Naito A, Morozumi M, Hatano T, Ogawa Y (2002) Association of vitamin D receptor gene polymorphism with urolithiasis. J Urol 167: 2188

    CAS  PubMed  Google Scholar 

  17. Picado-Leonard J, Miller WL (1987) Cloning and sequence of the human gene for P450c17 (steroid 17 α–hydroxylase/17,20 lyase): similarity with the gene for p450c21. DNA 6: 439

    CAS  PubMed  Google Scholar 

  18. Scheid C, Koul H, Hill WA, Luber-Narod J, Johnassen J, Honeyman T, Kennington L, Kohli R, Hodapp J, Ayvzian P, Menon M (1996) Oxalate toxicity in LLC-Pk1 cells: role of free radicals. Kidney Int 49: 413

    CAS  PubMed  Google Scholar 

  19. Shintani S, Matsuo K, Crohin CC, McBride J, Tsuji T, Donoff RB, Posner M, Todd R, Wong DTW (1999) Intragenic mutation analysis of the human epidermal growth factor receptor (EGFR) gene in malignant human oral keratinocytes. Cancer Res 59: 4142

    CAS  PubMed  Google Scholar 

  20. Thamilselvan S, Byer KJ, Hackett RL, Khan SR (2000) Free radical scavengers, catalase and superoxide dismutase provide protection from oxalate-associated injury to LLC-PK1 and MDCK cells. J Urol 164: 224

    CAS  PubMed  Google Scholar 

  21. Van Aswegen CH, Hurter P, Van der Merwe CA, Du Plessis DJ (1992) The relationship between total urinary testosterone and renal calculi. Urol Res 17: 181

    Google Scholar 

  22. Vu TH, Yballe C, Boonyanit S, Hoffman AR (1995) Insulin-like growth factor II in uterine smooth-muscle tumors: maintenance of genomic imprinting in leiomyosarcoma and loss of imprinting in leiomyosarcoma. J Clin Endocrinol Metab 80: 1670

    CAS  PubMed  Google Scholar 

  23. Watson CJ, Webb NJA, Bottomley MJ, Brenchley PE (2000) Identification of polymorphisms within the vascular endothelial growth factor (VEGF) gene: correlation with variation in VEGF protein production. Cytokine 12: 1232

    Article  CAS  PubMed  Google Scholar 

  24. Winter DL, Hanlon AL, Raysor SL, Watkins-Bruner D, Pinover WH, Hanks GE, Tricoli JV (2001) Plasma levels of IGF-1, IGF-2 andIGFBP-3 in white and African-American men at increased risk of prostate cancer. Urology 58: 614

    Article  CAS  PubMed  Google Scholar 

  25. Yarden Y, Ullrich A (1988) Growth factor receptor tyrosine kinases. Annu Rev Biochem 57: 443

    Google Scholar 

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Acknowledgement

This study was supported by a grant from the China Medical College Hospital (DMR-92-069).

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Authors and Affiliations

  1. Department of Urology, China Medical College Hospital, Taichung, Taiwan

    Wen-Chi Chen & Hsi-Chin Wu

  2. Department of Medical Genetics, China Medical College Hospital, Taichung, Taiwan

    Wen-Chi Chen, Huey-Yi Chen, Mei-Chen Wu, Cheng-Der Hsu & Fuu-Jen Tsai

  3. Department of Obstetric and Gynecology, China Medical College Hospital, Taichung, Taiwan

    Huey-Yi Chen

  4. Department of Pediatrics, China Medical College Hospital, Taichung, Taiwan

    Fuu-Jen Tsai

  5. 2 Yu-Der Road, Taichung, 404, Taiwan

    Fuu-Jen Tsai

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  1. Wen-Chi Chen
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Correspondence to Fuu-Jen Tsai.

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Chen, WC., Chen, HY., Wu, HC. et al. Vascular endothelial growth factor gene polymorphism is associated with calcium oxalate stone disease. Urol Res 31, 218–222 (2003). https://doi.org/10.1007/s00240-003-0325-2

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  • DOI: https://doi.org/10.1007/s00240-003-0325-2

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