Roles of Three Common VEGF Polymorphisms in the Risk of Age-Related Macular Degeneration

Abstract

Associations between vascular endothelial growth factor (VEGF) polymorphisms (rs833061, rs1413711, and rs3025039) and risk of age-related macular degeneration (AMD) have been extensively studied, but the currently available results are contentious rather than conclusive. Therefore, we performed the present metaanalysis to further assess the associations. Literature search in PubMed, Embase, and Web of Science databases was conducted until April 2013. The strength of the associations between VEGF polymorphisms and AMD risk was estimated by pooled odds ratios (ORs) and 95% confidence intervals (CIs). Both models of fixed effects and random effects were performed to summarize the pooled ORs. All data were analyzed by Stata software 12.0. The meta-analysis results based on nine case-control studies with 2427 cases and 2037 controls showed that rs833061 had protective effects on AMD risk (TT vs. CT + CC: OR = 0.58, 95% CI = 0.41-0.81), whereas rs1413711 (TT vs. CT + CC: OR = 1.46, 95% CI = 1.10-1.93) and rs3025039 (TT vs. CC: OR = 1.87, 95% CI = 1.15-3.02; TT vs. CT + CC: OR = 2.09, 95% CI = 1.30-3.37) represented as risk factors for AMD. Subgroup analysis by ethnicity suggested significantly reduced risk in Caucasians (TT vs. CT + CC: OR = 0.60, 95% CI = 0.36-0.99; T vs. C: OR = 0.89, 95% CI = 0.78-1.00) and Asians (TT + CT vs. CC: OR = 0.57, 95% CI = 0.34-0.96; TT vs. CT + CC: OR = 0.54, 95% CI = 0.33-0.90) for rs833061, yet elevated risk in Caucasians (TT vs. CT + CC: OR = 2.05, 95% CI = 1.24-3.38) for rs1413711 and in Asians (TT vs. CC: OR = 2.06, 95% CI = 1.24-3.43; TT vs. CC: OR = 2.34, 95% CI = 1.42-3.89) for rs3025039. In stratified analysis by type of AMD, rs833061 was observed to decrease wet AMD risk, while rs1413711 and rs3025039 were found to increase the risk of wet AMD. Based on the currently available data, this meta-analysis suggests that the VEGF polymorphisms may be associated with risk of AMD, particularly wet AMD.

Association between Vascular Endothelial Growth Factor Polymorphisms and Age-Related Macular Degeneration: An Updated Meta-Analysis

“…Although genetic variability of the VEGF gene may have a critical role in determining AMD risk, evidence by studies on small or moderate sample sizes remain ambiguous. These contentious results were also reported by recently published meta-analyses [21–23]. …”

Influence of VEGF-C936T genetic variant on age-related macular degeneration

“…Exudative AMD is characterized by geographic atrophy and choroidal neovascularization and involves the abnormal growth of neovessels from the choriocapillaris layer through breaks in the Bruch's membrane and retinal pigment epithelium (3) . Fenestrated neovessels allow the extravasation of fluids, lipids, and blood below and within the retina leading to the deterioration of central vision (4,5) . Clinically, AMD leads to clinically important functional visual loss and reduced quality of life, which are often underestimated (6) .…”

“…In addition, studies have provided evidence indicating the important role of genetic factors in the physiopathology of AMD (7) . Recently, a number of studies have evaluated the relationship between vascular endothelial growth factor (VEGF) polymorphisms and AMD genetic susceptibility variants (4) . The VEGF glycopeptide family includes the subgroups VEGF-A, VEGF-B, VEGF-C, VEGF-D, VEGF-E, and placental growth factor (PGF).…”

“…In the present study, we investigated a SNP consisting of replacement of a cytosine by a thymine at position 936 (C936T-rs3025039) within the untranslated region 3'UTR of the VEGF gene. This polymorphism has been shown to modulate VEGF-A expression (8) ; however, there have been conflicting results from diverse ethnic populations regarding its association with AMD (4) . Accordingly, the objective of the present study was to evaluate the associations between the VEGF-C936T polymorphism and serum VEGF levels, lifestyle, and demographic parameters in patients with AMD.…”

NETWORK APPROACH TO ANALYSIS OF QUANTITATIVE TRAIT LOCI FOR TUMOR NECROSIS FACTOR (TNFα-863, TNFα-308, TNFα-238), VASCULAR ENDOTHELIAL GROWTH FACTOR (VEGF-2578, VEGF+936) AND MATRIX METALLOPROTEINASE (Ммр2-1306, Ммр3-1171, Ммр9-1569) GENES IN AGERELATED MACULAR DEGENERATION

“…торного региона гена с влажной формой ВМД для китайской популяции [22] не подтверждается другими исследованиями в этой же популяции и не сохраняется для европейских популяций [11,12,23,31]. Эти данные подтверждаются и резуль-татами исследования в нашей группе пациентов.…”