DNA Sequence Variation In The VEGF Gene And Plasma VEGF Protein Levels

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Vascular endothelial growth factor (VEGF) is a potent endothelial cell mitogen involved in the process of angiogenesis. VEGF has been shown to be influenced by exercise and our laboratory has previously identified associations between DNA sequence variation in the VEGF gene and skeletal muscle capillarity and maximal oxygen consumption. PURPOSE The aim of this project was to determine if DNA sequence variation in the VEGF gene is associated with plasma VEGF protein levels. METHODS Subjects included 75 healthy, sedentary men and women, 50–75 years of age. Genomic DNA was extracted from peripheral lymphocytes and RFLP genotyping was performed on the C-2578A, G-634C, C-7T, and C936T variants in the VEGF gene. RESULTS The G-634C and C936T polymorphisms did not appear to be associated with plasma VEGF protein levels. Subjects of AA genotype at the C-2578A polymorphism exhibited ∼54% higher plasma VEGF protein levels than did subjects of AC or CC genotype (29.1±4.5 vs. 18.9±1.9 and 18.8±2.3, respectively, p < 0.05). Subjects of CC genotype at the C-7T polymorphism exhibited ∼28% lower plasma VEGF levels than did carriers of the T-allele (CT and TT genotype) (17.5±1.7 vs. 24.4±2.4, respectively, P = 0.02). CONCLUSIONS DNA sequence variation in the VEGF gene appears to be associated with circulating plasma VEGF levels in older men and women. Supported by NIH AG17474, AG15389, AG22791, and T32-A00268.