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

Alvita Vilkeviciute,Rasa Liutkeviciene,Loresa Kriauciuniene,Dzastina Cebatoriene

doi:10.3390/cells11060996

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.

Highlights

Age-related macular degeneration (AMD) is widely described as a multifactorial, progressive, neurodegenerative disease of the macula, causing loss of visual functions leading to blindness
Regarding the significant associations and conflicting results between genetic markers and AMD [22] in previous studies, we aimed to investigate the associations between four single nucleotide polymorphisms (SNPs) in vascular endothelial growth factor A (VEGFA) (OMIM* 192240), and VEGF-A and VEGFR-2/KDR protein roles in AMD in the Caucasian population to focus on a potential tool for early diagnosis
Three SNPs were in Hardy–Weinberg equilibrium (HWE) (p > 0.05), but rs1570360 did not conform the HWE requirements (p < 0.001) (Table 2)

Summary

Introduction

Age-related macular degeneration (AMD) is widely described as a multifactorial, progressive, neurodegenerative disease of the macula, causing loss of visual functions leading to blindness. Most eye function impairments are associated with age-related alterations and, together with the other risk factors such as environmental and genetic factors, lead to severe eye conditions [2]. Exponential population ageing is a recent worldwide problem affecting human health, including eye diseases. It is known that AMD affects about 10% of people older than 65 years and more than 25%. Of people older than 75 years in developed countries [2]. The previous study’s projection shows that the number of people with early AMD will increase up to 21.5 million and late AMD up to 4.8 million in Europe [3], while worldwide the numbers are expected to increase dramatically, even up to 288 million in 2040 [3]

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