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N. H. Tinkham, Z. Tong, D. Gibbs, L. Luo, J. Harmon, J. Buehler, Z. Yang, K. Zhang; Evaluation of The Association of a Specific VEGF Gene Polymorphism With Diabetic Retinopathy, Neuropathy, and Nephropathy in Type 2 Diabetics. Invest. Ophthalmol. Vis. Sci. 2008;49(13):1304. doi: https://doi.org/.
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Microvascular complications such as nephropathy, neuropathy, and retinopathy are the most significant causes of diabetic morbidity and mortality. Diabetic retinopathy (DR) is a common cause of visual loss in the western world. Vascular endothelial growth factor (VEGF) is a potent vascular permeability and angiogenic factor that has been associated with proliferative diabetic retinopathy (PDR) and prior studies have linked specific polymorphisms with PDR. However, less data exists evaluating the association of rs1413711 in the VEGF gene with nephropathy and neuropathy. The purpose of this study is to evaluate the association of rs1413711 in a Utah cohort with diabetic nephropathy, neuropathy, and retinopathy.
A case-control study was performed and cases of diabetic complications ( 387 neuropathy, 171 nephropathy, and 396 DR with its various subtypes) and 161 controls (type 2 diabetics with 10+years and no DR) were genotyped for a single nucleotide polymorphism (SNP rs1413711) in the promoter region of VEGF. Each patient underwent a clinical exam. DNA was extracted from peripheral blood leukocytes and the specific regions of the VEGF polymorphism were amplified by using site specific primers. Samples were analyzed using GeneScan Analysis on the ABI PRISM 3700 and results were confirmed by gene sequencing. Association was performed using Pearson’s X2 and Haploview.
Individual analysis of each diabetic complication (neuropathy, nephropathy, and retinopathy) and their association with each other and the VEGF polymorphism revealed that the G allele at rs1413711 was significantly associated with DR and was not associated with neuropathy or nephropathy. The G allele frequency was found to be 0.567 in cases (subjects with DR) and 0.500 in controls (p=0.013).
The rs1413711 SNP on the VEGF gene does not appear to be associated with diabetic neuropathy or nephropathy, but may influence the transcription of VEGF leading to DR. A large samples size and replication are required to validate these preliminary findings. Increased understanding of patient risk for disease complications may help physicians provide better individualized care in the future.
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