The aim of this work was to study for the first time in Romania Insertion/Deletion (I/D) polymorphism of the Vascular Endothelial Growth Factor (VEGF) gene in a group of patients with established type 2 diabetes mellitus (DM) and diabetic peripheral neuropathy (DPN) compared with a control group.
This was a case-control study consisting of a group of 84 patients with type 2 DM and DPN, diagnosed by clinical neurological examination and electrophysiological nerve conduction studies and a control group of 90 healthy volunteers. For deoxyribonucleic acid (DNA) isolation, a DNA purification kit from Zymo Research was used. In vitro amplification of DNA sequences was achieved by polymerase chain reaction (PCR). Selective in vitro amplification of a DNA fragment of known sequence is based on the principle of extension of a primer (“primer and PCR amplicon”). DNA fragments were separated by gel electrophoresis. For proper viewing and interpreting of agarose gels Vilber Lourmat system was used. D allele frequency of VEGF was significantly higher in patients with diabetic peripheral neuropathy (53.57%) compared with controls (25%), p=0.0001.
There is a positive association between I/D polymorphism of VEGF gene and the presence of diabetic peripheral polyneuropathy. Our study suggests that D allele of VEGF gene is a risk factor for the occurrence of DPN.
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1. Potra RA Kacso MI Bondor CI Gherman-Căprioară M. The predictive value of serum intercellular adhesion molecule 1 for the progression of diabetic kidney disease in type 2 diabetic patients. Rev Romana Med Lab. 2013;21(4):399-406. DOI: 10.2478/rrlm-2013-0045
2. Michael J. Fowler Microvascular and Macrovascular Complications of Diabetes. Clinical Diabetes. 2008;26(2):77-82. DOI: 10.2337/diaclin.26.2.77
3. Pradeepa R Anjana RM Unnikrishnan R Ganesan A Mohan V Rema M. Risk factors for microvascular complications of diabetes among South Indian subjects with type 2 diabetes-the Chennai Urban Rural Epidemiology Study (CURES) Eye Study-5. Diabetes Technol Ther. 2010;12(10):755-61. DOI: 10.1089/dia.2010.0069
4. Abbott CA Chaturvedi N Malik RA Salgami E Yates AP Pemberton PW et al. Explanations for the lower rates of diabetic neuropathy in Indian Asians Versus Europeans. Diabetes Care. 2010;33(6):1325-30. DOI: 10.2337/dc09-2067
5. Shweiki D Itin A Soffer D Keshet E. Vascular endothelial growth factor induced by hypoxia may mediate hypoxia-initiated angiogenesis. Nature. 1992;359:843-5. DOI: 10.1038/359843a0
6. Zhang X Bao S Hambly BD Gillies MC. Vascular endothelial growth factor-A: a multifunctional molecular player in diabetic retinopathy. Int J Biochem Cell Biol. 2009;41(12):2368-71. DOI: 10.1016/j.biocel.2009.07.011
7. Rosenstein JM Krum JM Ruhrberg C. VEGF in the nervous system. Organogenesis. 2010;6(2):107-14.DOI: 10.4161/org.6.2.11687
8. Ropper AH Gorson KC Gooch CL Weinberg DH Pieczek A Ware JH et al. Vascular endothelial growth factor gene transfer for diabetic polyneuropathy: a randomized double-blinded trial. Ann Neurol. 2009;65(4):386-93. DOI: 10.1002/ana.21675
9. Isner JM. Tissue responses to ischemia: local and remote responses for preserving perfusion of ischemic muscle. J Clin Invest. 2000;106:615-9. DOI: 10.1172/ JCI10961
10. Giacca M Zacchigna S. VEGF gene therapy: therapeutic angiogenesis in the clinic and beyond. Gene Ther. 2012;19(6):622-9. DOI: 10.1038/gt.2012.17
11. Duh E Aiello LP. Vascular endothelial growth factor and diabetes: the agonist versus antagonist paradox.Diabetes. 1999; 48:1899-906. DOI: 10.2337/diabetes.48.10.1899
12. Aiello LP Wong JS. Role of vascular endothelial growth factor in diabetic vascular complications. Kidney Int Suppl. 2000;77:S113-9. DOI: 10.1046/j.1523-1755.2000.07718.x
13. Leinninger GM Vincent AM Feldman EL. The role of growth factors in diabetic peripheral neuropathy. J Peripher Nerv Syst. 2004;9:26-53. DOI: 10.1111/j.1085-9489.2004.09105.x
14. Tavakkoly-Bazzaz J Amoli MM Pravica V Chandrasecaran R Boulton AJ Larijani B et al. VEGF gene polymorphism association with diabetic neuropathy.Mol Biol Rep. 2010;37:3625-30. DOI: 10.1007/ s11033-010-0013-6
15. Quattrini C Jeziorska M Boulton AJ Malik RA. Reduced vascular endothelial growth factor expression and intra-epidermal nerve fiber loss in human diabetic neuropathy. Diabetes Care. 2008;31(1):140-5. DOI: 10.2337/dc07-1556
16. Buraczynska M Ksiazek P Baranowicz-Gaszczyk I Jozwiak L. Association of the VEGF gene polymorphism with diabetic retinopathy in type 2 diabetic patients.Nephrol Dial Transplant. 2007;22(3):827-32.DOI: 10.1093/ndt/gfl641
17. Stevens A Soden J Brenchley PE Ralph S Ray DW.Haplotype analysis of the polymorphic human vascular endothelial growth factor gene promoter. Cancer Res. 2003;63(4):812-6.
18. He Y Ni J Chen S Jiang Y Jia S Gao Y. The vascular endothelial growth factor-2549 insertion/deletion polymorphism is not associated with susceptibility to hepatocellular carcinoma in Chinese. DNA Cell Biol. 2010;29(7):393-6. DOI: 10.1089/dna.2009.1015
19. Ropper AH1 Gorson KC Gooch CL Weinberg DH Pieczek A Ware JH et al. Vascular endothelial growth factor gene transfer for diabetic polyneuropathy: a randomized double-blinded trial. Ann Neurol. 2009;65(4):386-93. DOI: 10.1002/ana.21675
20. Deguchi T Hashiguchi T Horinouchi S Uto T Oku H Kimura K et al. Serum VEGF increases in diabetic polyneuropathy particularly in the neurologically active symptomatic stage. Diabetic Medicine. 2009;26(3):247-52. DOI: 10.1111/j.1464-5491.2009.02680.x
21. Yang B Cross DF Ollerenshaw M Millward BA Demaine AG. Polymorphisms of the vascular endothelial growth factor and susceptibility to diabetic microvascular complications in patients with type 1 diabetes mellitus.J Diabetes Complications. 2003;17(1):1-6. DOI: 10.1016/S1056-8727(02)00181-2
22. Kacso MI Trifa PA Popp AR Bondor IC Farcas FM Lenghel RA et al. Adiponectin gene 45T>G polymorphism is not associated to plasma adiponectin in a cohort of patients with type 2 diabetes from Romania. Rev Romana Med Lab. 2012;20(1):73-9.
23. Moldovan R Kacsò I Gherman-Căprioară M. Relationship between soluble intercellular adhesion molecule 1 and clinically manifest cardiovascular disease in diabetic chronic hemodialysis patients. Rev Romana Med Lab. 2012;20(4):353-61.