Influence of VEGFA gene polymorphisms rs2010963 and rs699947 on clinical and laboratory indicators in diabetic retinopathy among patients with type 2 diabetes mellitus

Abstract

Background. A key factor of neoangiogenesis deve­lopment in diabetic retinopathy (DR) among patients with type 2 diabetes mellitus (DM) is vascular endothelial growth factor A (VEGFA). The important role of genetic polymorphisms of the VEGFA gene indicates a number of studies and meta-analyzes, that have shown their association with DR, especially with its proliferative variant, which varies in different populations. Accordingly, the purpose of this work was to find out the influence of the polymorphic genotypes rs2010963 and rs699947 of the VEGFA gene on clinical and laboratory parameters of DR in DM patients from Ukrainian population. Materials and methods. The study involved 302 patients with type 2 diabetes mellitus and DR. Diagnosis was established according to the international clinical classification adopted by the American Academy of Ophthalmology (2003). The control group consisted of 98 people who did not have DM and DR, as well as other ophthalmic diseases. All patients were operated on cataract. In the intraocular fluid collected during the surgery, the VEGFA content was determined by the immunoassay method. Analysis of the polymorphic DNA loci of the VEGFA gene: rs2010963 and rs699947 was performed in a real time polymerase chain reaction using TaqMan Mutation Detection Assays (Thermo Fisher Scientific, USA). Results. An analysis of the study results showed that rs2010963 polymorphism had an effect on the intraocular fluid VEGFA level (maximum — under the C/C risk genotype). This polymorphism was related to the sex (the genotype C/C was more common in men than in women: 3 : 1), the presence of proliferative DR (most often was determined by the presence of the genotype C/C: 45.4 %) and neovascularization of the optic disc (most often determined by the pre­sence of heterozygotes G/C: 21.4 %). Polymorphism rs699947 had an effect on the visual acuity (the minimum was available in the genotype C/C), the thickness of the retina (the maximum value — in the genotype C/C), the content of VEGFA in intraocular fluid (maximum level — in the genotype C/C), as well as the presence of proliferative DR and hemophthalm (most often determined by the presence of the genotype C/C, respectively: 44.7 and 27.7 %). Conclusions. The pathogenetic effect of the risk of genotype C/C rs2010963 was more often detected in men, realized due to the high level of VEGFA in intraocular fluid and manifested by the maximum incidence of proliferative DR. The pathogenetic effect of the genotype C/C rs699947 risk has also been realized due to the high intraocular VEGFA level, resulting in decreased visual acuity and retinal thickening and manifested as the maximum rate of proliferative DR and hemophthalm.

Keywords

• diabetic retinopathy
• VEGFA gene polymorphism
• rs2010963
• rs699947