VEGFA Haplotype and VEGF-A and VEGF-R2 Protein Associations with Exudative Age-Related Macular Degeneration

Abstract

Our study aimed to reveal the associations between VEGFA SNPs (rs1570360, rs699947, rs3025033, and rs2146323), their haplotypes, VEGF-A and VEGF-R2 serum concentrations, and early and exudative AMD. A total of 339 subjects with early AMD and 419 with exudative AMD groups, and 374 healthy subjects, were genotyped for four VEGFA SNPs (rs1570360, rs699947, rs3025033, and rs2146323). VEGF-A and VEGFR-2 serum concentrations were measured in exudative AMD and controls. The results revealed that rs3025033 G allele was significantly associated with lower odds of exudative AMD under the dominant model (OR = 0.67; 95% CI: 0.49–0.80; p = 0.0088) and additive (OR = 0.7; 95% CI: 0.54–0.90; p = 0.0058) models after Bonferroni correction. In the female group, rs3025033 AG genotype was associated with exudative AMD under the codominant model (OR = 0.57; 95% CI: 0.37–0.87; p = 0.009) and G allele under the dominant (OR = 0.55; 95% CI: 0.37–0.82; p = 0.0032) and additive models (OR = 0.60; 95% CI: 0.42–0.84; p = 0.0028). Haplotype analysis revealed that individuals carrying rs1570360, rs699947, rs3025033, and rs2146323 haplotype A-A-G-A had decreased risk of exudative AMD (OR = 0.46, 95% CI: 0.23–0.90; p = 0.023). The VEGF-A and VEGF-R2 serum concentrations did not differ between study groups; we found that patients with exudative AMD carrying at least one C allele at rs699947 have statistically significantly higher VEGF-A serum concentrations compared to AA genotype carriers (485.95 (945.93) vs. 194.97 (-), respectively, p = 0.046). In conclusion, we found that VEGFA rs3025033 and haplotype rs1570360A-rs699947A-rs3025033G- rs2146323A play a protective role for exudative AMD in the Caucasian population. Furthermore, rs699947 is associated with elevated VEGF-A serum concentrations in exudative AMD.

Molecular Genetic Mechanisms in Age-Related Macular Degeneration

“…Multiple VEGF-A variants have been identified, most of which surprisingly have not been strongly or consistently associated with AMD [ 38 , 262 ]. However, the VEGF-A rs3025033 variant and haplotype rs1570360A-rs699947A-rs3025033G-rs2146323A have recently been associated with a lower risk of neovascular AMD [ 263 ]. Conversely, the VEGF-A rs3025039 C-allele may increase the risk of AMD, although apparently only in the context of the rs1048661 lysine oxidase 1 ( LOXL1 ) gene variant [ 264 ].…”

“…rs1570360A-rs699947A-rs3025033G-rs2146323A have recently been associated with a lower risk of neovascular AMD [263]. Conversely, the VEGF-A rs3025039 C-allele may increase the risk of AMD, although apparently only in the context of the rs1048661 lysine oxidase 1 (LOXL1) gene variant [264].…”

Exudative Age-Related Macular Degeneration: Association between Treatment Efficacy and Single-Nucleotide Variants in RAD51B, TRIB1, COL8A1, COL10A1, IL-9, IL-10, and VEGFA Genes

“…Deoxyribonucleic acid (DNA) extraction and the genotyping of eighteen single-nucleotide variants (SNVs) were conducted, targeting RAD51B (rs8017304 and rs2588809), TRIB1 (rs6987702 and rs4351379), COL8A1 (rs13095226), COL10A1 (rs1064583), IL-9 (rs1859430, rs2069870, rs11741137, rs2069885, and rs2069884), IL-10 (rs1800871, rs1800872, and rs1800896), and VEGFA (rs1570360, rs699947, rs3025033, and rs2146323). These procedures were performed at the Laboratory of Ophthalmology, Neuroscience Institute, Lithuanian University of Health Sciences, utilizing predesigned TaqManTM Genotyping assays from Thermo Fisher Scientific, Pleasanton, CA, USA, following the manufacturer's guidelines and as previously described in our publications [38][39][40].…”