Contribution of VEGF polymorphisms to variation in VEGF serum levels in a healthy population

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Abstract

Objective. Vascular endothelial growth factor (VEGF) is a pro-angiogenic factor. Variability in VEGF expression, induced by specific VEGFA variants, are involved in angiogenesis-related disorders. This study examined the genotype distribution and functional role (VEGF expression) of rs699947, rs833061, rs1570360, rs2010963, rs833068, rs833070, rs3025020, and rs3025039 VEGFA variants and their haplotypes in 519 healthy Bahraini individuals of both genders. Methods and results. The distribution of the eight VEGFA polymorphisms screened was in Hardy-Weinberg equilibrium. The minor allele frequencies of rs699947 (0.42), rs833061 (0.32), rs1570360 (0.31), rs2010963 (0.33), rs833068 (0.37), rs833070 (0.42), rs3025020 (0.33), and rs3025039 (0.13) were generally compared to those established for Caucasians. Of the variants tested, rs3025020 was associated with increased VEGF serum levels (p=0.019), while rs3025039 was associated with decreased levels (p=0.038). Linkage analysis identified two VEGFA blocks, the first, spanning 16 kb, was not associated with altered VEGF levels, while the second, spanning 3 kb containing rs3025020 and rs3025039, was linked with higher VEGF expression, of which the -583T/ +936T haplotype (p=0.008) was linked with higher VEGF levels compared to the -583C/ +936C (all wild-type) haplotype. Conclusion. These results support the association of rs30250202 and rs3025039, and specific VEGF haplotypes, with altered VEGF serum levels, although the exact functional mechanisms remain to be elucidated.

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Al-Habboubi, H. H., Sater, M. S., Almawi, A. W., Al-Khateeb, G. M., & Almawi, W. Y. (2011). Contribution of VEGF polymorphisms to variation in VEGF serum levels in a healthy population. European Cytokine Network, 22(3), 154–158. https://doi.org/10.1684/ecn.2011.0289

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