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

Abstract

Age-related macular degeneration (AMD) is the most common cause of blindness in elderly people worldwide and the major degenerative disease of the retina that leads to progressive impairment of central vision. Several polymorphisms in different genes have been proposed as factors that increase the disease susceptibility. The aim of the present study is to carry out a systematic review and an updated meta-analysis in order to summarize the current published studies and to evaluate the associations between four common vascular endothelial growth factor (VEGF) polymorphisms (rs833061, rs1413711, rs3025039, and rs2010963) and AMD risk, also stratifying for AMD subtypes and ethnicity. A systematic literature search in the Medline database, using PubMed, was carried out for epidemiological studies, published before June 2016. Associations of VEGF polymorphisms with AMD were estimated by calculating pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) based on different models. Twelve articles were included in the analysis. The present meta-analysis constitutes a useful guide for readers to study AMD and adds new evidence to the growing literature on the role of VEGF polymorphisms in the risk of AMD. Significant associations with AMD risk were showed for rs833061, rs1413711, and rs3025039 polymorphisms but not for rs2010963.

The role of hypoxia-inducible factors in neovascular age-related macular degeneration: a gene therapy perspective

“…Etiologically, AMD is a multifactorial disease. Genetic variants associated with AMD include complement factor (CF)H [11] and CFH-related genes 1 to 5 [12], complement protein (C)3 [13], C9 [14], age-related maculopathy susceptibility (ARMS)2 gene [15], and the vascular endothelial growth factor (VEGF) and VEGF receptor (VEGFR) axis [16,17]. In addition, other genetic variants have shown a causal link to AMD, such as tissue inhibitor metalloproteinase (TIMP) 3 [18], fibrillin [19], collagen 4A3, and metalloproteinase (MMP) 19 and − 9 [20].…”

Complement System and Age-Related Macular Degeneration: Implications of Gene-Environment Interaction for Preventive and Personalized Medicine

“…In addition to the effect of modifiable factors, genetic variants confer about 60% of the attributable risk [ 30 ], with at least 34 genomic loci implicated in AMD pathogenesis [ 31 ]. Genetic risk factors associated with AMD susceptibility include polymorphisms in complement factor H ( CFH ) [ 32 ], age-related maculopathy susceptibility 2 ( ARMS2 ) [ 33 ], apolipoprotein E ( APOE ) [ 34 ], and vascular endothelial growth factor ( VEGF) [ 35 ]. Above all, the discovery of genetic variants in components of the complement system indicated the potential role of local inflammation and complement regulation in the pathogenesis of AMD [ 36 ].…”

The association between complement factor H rs1061170 polymorphism and age‐related macular degeneration: a comprehensive meta‐analysis stratified by stage of disease and ethnicity

“…Genetic variants associated with the susceptibility to AMD are especially involved in complement system activity, lipid metabolism and angiogenesis (Fritsche et al. , ; Barchitta & Maugeri ). More recently, the effect of additional polymorphisms, as well as the dysregulation of microRNAs, has been involved in both pathological CNV and functional response to treatment against neovascular AMD (Askou et al.…”