GENETIC CRITERIA FOR ANTI-ANGIOGENIC THERAPY FOR TREATMENT OF DIABETIC MACULAR EDEMA
Anzhella Zhanovna FURSOVA1,2, Nadezhda Viktorovna CHUBAR1, Mikhail Sergeevich TARASOV1, Mariya Andreevna VASILYEVA1, Sarafroz Aftondilkizi ERKINOVA3,4, Aleksandra Sergeevna SHADRINA2,4, Ekaterina Alekseevna SOKOLOVA3,4, Maksim Leonidovich FILIPENKO3,4
1Novosibirsk State Region Hospital
2Novosibirsk State Medical University of Minzdrav of Russia
3Institute of Chemical Biology and Fundamental Medicine of SB RAS
4Novosibirsk State University
Keywords: диффузный макулярный отек, оптическая когерентная томография, фовеолярная толщина сетчатки, ранибизумаб, diffuse macular edema, optical coherence tomography, foveolar thickness of retina, ranibizumab
Abstract
Apart from already established clinical factors, the polymorphic loci of the VEGF gene and its VEGFR2 receptor can have a significant effect on the response to anti-VEGF therapy of diabetic macular edema. The aim was to study the association of single nucleotide polymorphic loci of VEGF and VEGFR2 genes, as well as functional and anatomical parameters with response to ranibizumab therapy in patients with diabetic macular edema. Material and methods. The study includes 145 patients (145 eyes) with diabetic macular edema. All the patients are divided into 2 groups: a positive response (A) and no response to angiogenic therapy (B). The positive response (group A) was the presence of a reduction of at least 10 % of the foveolar thickness (FT) from the baseline according to the OST data. In addition, the response category was assessed: a good response (A1): a reduction in FT by more than 25 %, and an increase in MCHO by more than 5 letters of ETDRS and a poor response (group A2): a reduction in FT of 10-25 % and an increase in MCRI by less than 5 letters ETDRS. Genomic DNA was selected from leukocytes in venous blood, genotyping was performed by real-time PCR using probes of hydrolysing samples. Results. 45 (33.6 %) patients demonstrated a good response (group A1) to therapy and 89 (66.4 %) had a «bad» response (group A2). In group A1, the decrease in FT occurred on average by 25.61 %, the increase in MHC was 0.21 ± 0.07, while in group A2, the visual acuity increased by 0.05, with the thickness of the retina reduction by 74.1 μm (19, 5 %). Rs3025039 of the VEGFA gene is associated with the change in PTC ( p = 0.02). The decrease in the volume of the macula is associated with the allele C rs2010963 of the VEGFA gene ( p = 0.03). For the carriers of the T allele, the locus rs3025039 of the VEGFA gene, on the contrary, shows a lower value of the decrease in the volume of the macula ( p = 0.03). The patients with the T / T genotype of the polymorphic locus rs3025039 of the VEGFA gene statistically respond to anti-VEGF therapy significantly worse.
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