Interethnic Differences in the Distribution of Clinically Relevant Vascular Endothelial Growth Factor Genetic Polymorphisms

Abstract

Vascular endothelial growth factor (VEGF) is a homodimeric glycoprotein produced mostly in endothelial cells and its transcription is regulated by a variety of growth factors and cytokines. VEGF plays many relevant roles, and three functional polymorphisms in the promoter region of the VEGF gene (C-2578A, G-1154A, and G-634C) have been associated with disease conditions. Although some studies suggest that interethnic differences exist in the distribution of these variants, no previous study has examined this hypothesis in admixed populations. We examined the distribution of these three clinically relevant VEGF single-nucleotide polymorphisms in 175 white and 185 black subjects. We have also estimated the haplotype distribution and assessed associations between these variants. Although the A-2578 and A-1154 variants were more common in whites (39% and 29%, respectively) than in blacks (29% and 16%, respectively; both p < 0.05), no significant interethnic differences were found with regards to the G-634C polymorphism. While the haplotype including the C-2578, G-1154, and G-634 variants was the most common in both ethnic groups, it was more common in blacks than in whites (p < 0.05). The haplotype including the C-2578, A-1154, and G-634 alleles and the haplotype including the C-2578, A-1154, and C-634 alleles were more common in whites than in blacks (both p < 0.05). These results show marked interethnic differences in the distribution of genetic variants of VEGF that may explain, at least in part, interethnic disparities in the susceptibility to cardiovascular diseases.

Functional VEGF haplotypes affect the susceptibility to hypertension

“…21,22 In the substudy 1, there are clear interethnic differences in the distribution of VEGF genetic variants, as previously shown. 16 In fact, our results in blacks and whites are very similar to those previously reported in these two ethnic groups. 16 These results confirm the relevance of considering population stratification due to ethnic diversity in association studies, which may cause unbalanced distribution of genetic variants and decrease the power of association studies.…”

“…16 In fact, our results in blacks and whites are very similar to those previously reported in these two ethnic groups. 16 These results confirm the relevance of considering population stratification due to ethnic diversity in association studies, which may cause unbalanced distribution of genetic variants and decrease the power of association studies. 23 In the present study, ethnicity has been defined with basis on self-reporting.…”

“…Table 2 shows the results of the single-locus analysis for the substudy 1. Because there are interethnic differences in the distribution of VEGF gene variants, 16 we analyzed the results according to ethnicity. In both ethnic groups (blacks and whites), we found no significant differences in genotypes or alleles distributions for the three VEGF polymorphisms when NT and HTN subjects were compared (Table 2; all P40.05).…”

“…This comparison was carried separately in black and white subjects because interethnic differences exist in the distribution of VEGF variants. 16 The substudy 2 aimed at comparing the distribution of VEGF genetic variants in HTN patients, who are resistant to conventional antihypertensive therapy (resistant hypertensive (RHTN)), with those found in controlled HTN subjects and with NT healthy controls. This substudy could implicate VEGF polymorphisms in the pathophysiological mechanisms, leading to resistant hypertension.…”

Papel do fator de crescimento vascular endotelial na angiogênese e na retinopatia diabética

“…Ao avaliar três polimorfismos na região promotora do gene VEGF, -2578C/A (rs699947), -1154 G/A e -634C/ G, pesquisadores de Campinas/SP observaram que, embora as variantes -2578A e -1154A sejam mais comuns em brancos que em negros, não houve diferenças significativas interétnicas em relação ao polimorfismo -634C/G (56 No tratamento da RD, essas medicações são aplicadas dentro da cavidade vítrea. Em decorrência da curta duração do seu efeito, os antiVEGFs necessitariam de injeções intravítreas repetidas, o que aumentaria o risco de endoftalmite, aumento da pressão intraocular, rasgo de epitélio pigmentar, rasgo e descolamento de retina.…”