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The role of vascular endothelial growth factor +405 G/C polymorphism and albuminuria in patients with type 2 diabetes mellitus

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Abstract

Observations on the association between the vascular endothelial growth factor (VEGF) gene polymorphism and nephropathy have been inconsistent, which might be due to ethnic and geographical variations. Furthermore, the relationship between +405 G/C polymorphism and albuminuria in the diabetic population has not been sufficiently studied. The aim of this study was to evaluate for the first time the possible association between +405 G/C polymorphism and albuminuria in an population from Tehran of Iran. A total of 255 consecutive patients with type 2 diabetes and microalbuminuria (Group A) and 235 patients with type 2 diabetes and normoalbuminuria (Group B) were included. Polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) were used to detect the VEGF alleles. In univariate analysis, the groups were statistically similar in all variables except for HbA1c (8.53 ± 1.7 in Group A vs. 8.2 ± 1.73 in Group B; P = 0.034), 24-h urinary albumin (201.33 ± 84.8 in Group A vs. 22.88 ± 3.5 in Group B; P < 0.001), and the frequency of GG genotype (31% in Group A vs. 18.7% in Group B; P = 0.006). The GG genotype was the independent predictor of albuminuria [P = 0.014, OR = 1.771, 95% confidence interval (CI) = 1.124–2.790]. Our study showed that the G allele was not associated with albuminuria, but the GG genotype in the VEGF gene is independently associated with development of nephropathy in the our diabetic population.

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References

  1. Held PJ, Port FK, Webb RL et al (1991) The United States Renal Data System’s (1991) annual data report: an introduction. Am J Kidney Dis 18:1–16

    PubMed  CAS  Google Scholar 

  2. Kretzler M, Schroppel B, Merkle M et al (1998) Detection of multiple vascular endothelial growth factor splice isoforms in single glomerular podocytes. Kidney Int Suppl 67:S159–S161

    Article  PubMed  CAS  Google Scholar 

  3. Shulman K, Rosen S, Tognazzi K, Manseau EJ, Brown F (1996) Expression of vascular permeability factor (VPF/VEGF) is altered in many glomerular diseases. J Am Soc Nephrol 7:661–666

    PubMed  CAS  Google Scholar 

  4. Ziyadeh FN, Guo J (2004) Mediators of diabetic renal disease: the case for TGF-beta as the major mediator. J Am Soc Nephrol 15(Suppl 1):S55–S57

    Article  PubMed  CAS  Google Scholar 

  5. Singh DK, Winocour P, Farrington K (2008) Mechanisms of disease: the hypoxic tubular hypothesis of diabetic nephropathy. Nat Clin Pract Nephrol 4:216–226

    Article  PubMed  CAS  Google Scholar 

  6. Vasavada N, Agarwal R (2005) Role of oxidative stress in diabetic nephropathy. Adv Chronic Kidney Dis 12:146–154

    Article  PubMed  Google Scholar 

  7. Raptis AE, Viberti G (2001) Pathogenesis of diabetic nephropathy. Exp Clin Endocrinol Diabetes 109(Suppl 2):S424–S437

    Article  PubMed  CAS  Google Scholar 

  8. WuL W, Mayo LD, Dunbar JD et al (2000) Utilization of distinct signaling pathways by receptors for vascular endothelial cell growth factor and other mitogens in the induction of endothelial cell proliferation. J Biol Chem 275:5096–5103

    Google Scholar 

  9. Hohenstein B, Hausknecht B, Boehmer K et al (2006) Local VEGF activity but not VEGF expression is tightly regulated during diabetic nephropathy in man. Kidney Int 69:1654–1661

    Article  PubMed  CAS  Google Scholar 

  10. De Vriese AS, Tilton RG, Elger M et al (2001) Antibodies against vascular endothelial growth factor improve early renal dysfunction in experimental diabetes. J Am Soc Nephrol 12:993–1000

    PubMed  Google Scholar 

  11. Kanesaki Y, Suzuki D, Uehara G et al (2005) Vascular endothelial growth factor gene expression is correlated with glomerular neovascularization in human diabetic nephropathy. Am J Kidney Dis 45:288–294

    Article  PubMed  CAS  Google Scholar 

  12. Satchell SC, Harper SJ, Mathieson PW (2004) Angiopoietin 1 and vascular endothelial growth factor modulate human glomerular endothelial cell barrier properties. J Am Soc Nephrol 15:566–574

    Article  PubMed  CAS  Google Scholar 

  13. Tsilibary EC (2003) Microvascular basement membranes in diabetes mellitus. J Pathol 200:537–546

    Article  PubMed  CAS  Google Scholar 

  14. Sharma K, Ziyadeh FN (1995) Hyperglycemia and diabetic kidney disease. The case for transforming growth factor-beta as a key mediator. Diabetes 44:1139–1146

    Article  PubMed  CAS  Google Scholar 

  15. Flyvbjerg A, Dagnaes-Hansen F, De Vriese AS et al (2002) Amelioration of long-term renal changes in obese type 2 diabetic mice by a neutralizing vascular endothelial growth factor antibody. Diabetes 51:3090–3094

    Article  PubMed  CAS  Google Scholar 

  16. Wolf G, Chen S, Ziyadeh FN et al (2005) From the periphery of the glomerular capillary wall toward the center of disease: podocyte injury comes of age in diabetic nephropathy. Diabetes 54:1626–1634

    Article  PubMed  CAS  Google Scholar 

  17. Eremina V, Miner JH et al (2006) Vascular endothelial growth factor a signaling in the podocyte-endothelial compartment is required for mesangial cell migration and survival. J Am Soc Nephrol 17:724–735

    Article  PubMed  CAS  Google Scholar 

  18. Rutledge JC, Ng KF, Aung HH et al (2010) Role of triglyceride-rich lipoproteins in diabetic nephropathy. Nat Rev Nephrol 6:361–370

    Article  PubMed  CAS  Google Scholar 

  19. Adler S (2004) Diabetic nephropathy: linking histology, cell biology, and genetics. Kidney Int 66:2095–2106

    Article  PubMed  Google Scholar 

  20. American Diabetes Association (2005) Diagnosis and classification of diabetes mellitus. Diabetes Care 28:S37–S42

    Google Scholar 

  21. Gentilini D, Somigliana E, Vigano P et al (2008) The vascular endothelial growth factor 405G/C polymorphism in endometriosis. Hum Reprod 23(1):211–215

    Article  PubMed  CAS  Google Scholar 

  22. Ferrara N, Davis-Smyth T (1997) The biology of vascular endothelial growth factor. Endocr Rev 18:4–25

    Article  PubMed  CAS  Google Scholar 

  23. Murata T, Ishibashi K, Khalil A et al (1995) Vascular endothelial growth factor plays a role in hyperpermeability of diabetic retinal vessels. Ophthal Res 27:48–52

    Article  CAS  Google Scholar 

  24. Ferrara N (1995) Vascular endothelial growth factor: the trigger for neovascularization in the eye. Lab Invest 72:615–618

    PubMed  CAS  Google Scholar 

  25. Witmer AN, Vrensen GF, Van Noorden CJF et al (2003) Vascular endothelial growth factors and angiogenesis in eye disease. Prog Retin Eye Res 22:1–29

    Article  PubMed  CAS  Google Scholar 

  26. Summers AM, Coupes BM et al (2005) VEGF −460 genotype plays an important role in progression to chronic kidney disease stage 5. Nephrol Dial Transplant 20:2427–2432

    Article  PubMed  CAS  Google Scholar 

  27. SchrIjvers BF, Flyvbjerg A, De Vriese A (2004) The role of vascular endothelial growth factor (VEGF) in renal pathophysiology. Kidney Int 65(6):2003–2017

    Article  PubMed  CAS  Google Scholar 

  28. Cooper ME, Anderson S, Brenner BM et al (1998) Pathogenesis prevention and treatment of diabetic nephropathy. Lancet 352:213–219

    Article  PubMed  CAS  Google Scholar 

  29. Ichinose K, Kawasaki E, Eguchi K et al (2007) Recent advancement of understanding pathogenesis of type 1 diabetes and potential relevance to diabetic nephropathy. Am J Nephrol 27(6):554–564

    Article  PubMed  CAS  Google Scholar 

  30. Buraczynska M, Ksiazek P, Baranowicz-Gaszczyk I et al (2007) Association of the VEGF gene polymorphism with diabetic retinopathy in type 2 diabetes patients. Nephrol Dial Transplant 22:827–832

    Article  PubMed  CAS  Google Scholar 

  31. Ray D, Mishra M, Ralph S, Read J et al (2004) Association of the VEGF gene with proliferative diabetic retinopathy but not proteinuria in diabetes. Diabetes 53:861–864

    Article  PubMed  CAS  Google Scholar 

  32. Grone HJ, Miller JW, Adamis AP et al (1995) Angiogenesis and vascular endothelial growth factor (VEGF): is it relevant in renal patients? Nephrol Dial Transplant 10:761–763

    PubMed  CAS  Google Scholar 

  33. Awata T, Inoue K, Kurihara S et al (2002) A common polymorphism in the 50-untranslated region of the VEGF gene is associated with diabetic retinopathy in type 2 diabetes. Diabetes 51:1635–1639

    Article  PubMed  CAS  Google Scholar 

  34. De Vriese AS, Verbeuren TJ, Van de Voorde J et al (2000) Endothelial dysfunction in diabetes. Br J Pharmacol 130:963–974

    Article  PubMed  Google Scholar 

  35. Aiello LP, Wong J-S (2000) Role of vascular endothelial growth factor in diabetic vascular complications. Kidney Int Suppl 77:S113–S119

    Article  PubMed  CAS  Google Scholar 

  36. Doi K, Noiri E, Nakao A, Fujita T et al (2006) Functional polymorphisms in the vascular endothelial growth factor gene are associated with development of end-stage renal disease in males. J Am Soc Nephrol 17(3):823–830

    Article  PubMed  CAS  Google Scholar 

  37. Watson CJ, Webb NJA, Bottomley MJ et al (2000) Identification of polymorphisms within the vascular endothelial growth factor (VEGF) gene: correlation with variation in VEGF protein production. Cytokine 12:1232–1235

    Article  PubMed  CAS  Google Scholar 

  38. Cha DR, Kim NH, Yoon JW et al (2000) Role of vascular endothelial growth factor in diabetic nephropathy. Kidney Int Suppl 77:S104–S112

    Article  PubMed  CAS  Google Scholar 

  39. Chiarelli F, Spagnoli A, Basciani F et al (2000) Vascular endothelial growth factor (VEGF) in children, adolescents and young adults with type 1 diabetes mellitus: relation to glycaemic control and microvascular complications. Diabet Med 17:650–656

    Article  PubMed  CAS  Google Scholar 

  40. Tavakkoly-Bazzaz J, Amoli MM, Pravica V et al (2010) VEGF gene polymorphism association with diabetic neuropathy. Mol Biol Rep 37(7):3625–3630

    Article  PubMed  CAS  Google Scholar 

  41. Summers AM, Coupes BM, Brennan MF et al (2005) VEGF −460 genotype plays an important role in progression to chronic kidney disease stage 5. Nephrol Dial Transplant 20:2427–2432

    Article  PubMed  CAS  Google Scholar 

  42. Trevisan R, Viberti G (1995) Genetic factors in the development of diabetic nephropathy. J Lab Clin Med 126:342–349

    PubMed  CAS  Google Scholar 

  43. Pettitt DJ, Robbins DC et al (1990) Familial predisposition to renal disease in two generations of Pima Indians with type 2 (non-insulin-dependent) diabetes mellitus. Diabetologia 33:438–443

    Article  PubMed  CAS  Google Scholar 

  44. Lijima K, Yoshikawa N, Connolly DT et al (1993) Human mesangial cells and peripheral blood mononuclear cells produce vascular permeability factor. Kidney Int 44:959–966

    Article  Google Scholar 

  45. De Vriese AS, Tilton RG, Elger M et al (2001) Antibodies against vascular endothelial growth factor improve early renal dysfunction in experimental diabetes. J Am Soc Nephrol 12:993–1000

    PubMed  Google Scholar 

  46. Lenz T, Haak T, Malek J et al (2003) Vascular endothelial growth factor in diabetic nephropathy. Kidney Blood Press Res 26(5–6):338–343

    Google Scholar 

  47. Yang JW, Hutchinson IV, Shah T et al (2011) Gene polymorphism of vascular endothelial growth factor −1154 G>A is associated with hypertensive nephropathy in a Hispanic population. Mol Biol Rep 38(4):2417–2425

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The authors would like to thank Mr. Reza Safary for his helpful and the Department of Endocrinology and Metabolism Research Center (EMRC), Vali-e-Asr Hospital, Tehran University of Medical Sciences.

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Authors and Affiliations

  1. Department of Biochemistry, Faculty of Medicine, Ahvaz Jondi Shapour University of Medical Sciences, Ahvaz, Iran

    Abdolrahim Nikzamir

  2. Endocrinology and Metabolism Research Center (EMRC), Vali-Asr Hospital, Tehran University of Medical Sciences, Tehran, Iran

    Alireza Esteghamati

  3. Health Department, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran

    Amir Abbas Hammedian

  4. Research Center for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Touraj Mahmoudi

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  1. Abdolrahim Nikzamir
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  2. Alireza Esteghamati
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Correspondence to Abdolrahim Nikzamir.

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Nikzamir, A., Esteghamati, A., Hammedian, A.A. et al. The role of vascular endothelial growth factor +405 G/C polymorphism and albuminuria in patients with type 2 diabetes mellitus. Mol Biol Rep 39, 881–886 (2012). https://doi.org/10.1007/s11033-011-0812-4

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