The Role of SNPs in <i>IL1RL1</i> and <i>IL1RAP</i> Genes in Age-related Macular Degeneration Development and Treatment Efficacy

Vilkeviciute, Alvita; Bastikaityte, Neringa; Mockutė, Rūta; Čebatorienė, Džastina; Kriauciuniene, Loresa; Balčiūnienė, Vilma Jūratė; Žemaitienė, Reda; Liutkevičienė, Rasa

doi:10.21873/invivo.12059

Cited by 5 publications

(7 citation statements)

References 41 publications

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“…The best genetic model selection was based on the Akaike information criterion (AIC); therefore, the best genetic models had the lowest AIC values. We introduced an adjusted significance threshold for multiple comparisons alpha = 0.0125 (0.05/4, since we analyzed four SNPs in the VEGF-A gene) [28].…”

Section: Discussionmentioning

confidence: 99%

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

Vilkeviciute

Čebatorienė

Kriauciuniene

et al. 2022

Cells

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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.

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Section: Discussionmentioning

confidence: 99%

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

Vilkeviciute

Čebatorienė

Kriauciuniene

et al. 2022

Cells

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“…Sanjeewa et al research has shown that the APOE ε4 allele’s presence conferred significantly better visual functions after anti-VEGF treatment than did the ε2 allele [ 42 ]. Another study has shown that IL1RL1 rs1041973 might play a protective role against macular thickening in eAMD patients [ 28 ].…”

Section: Discussionmentioning

confidence: 99%

“…DNA extraction and genotyping was described in our previous research [ 27 , 28 ]. The DNA extraction and analysis of ABCA1 (rs1883025) and CYP4F2 (rs2108622) polymorphisms were carried out at the laboratory Ophthalmology at the Institute of Neuroscience of LUHS.…”

Section: Methodsmentioning

confidence: 99%

ABCA1 rs1883025 and CYP4F2 rs2108622 Gene Polymorphism Association with Age-Related Macular Degeneration and Anti-VEGF Treatment

et al. 2021

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Background and Objectives: The age-related macular degeneration (AMD) pathophysiology is multifactorial, as it consists of interactions between aging, genetic, and environmental factors. We aimed to determine a relationship between AMD and the genes controlling lipid metabolism, and to assess its association with treatment results. The purpose was to find the ABCA1 rs1883025 and CYP4F2 rs2108622 gene polymorphisms in patients with exudative AMD (eAMD) treated with anti-VEGF. Materials and Methods: The study enroled 104 patients with eAMD and 201 healthy persons in a control group. The genotyping of rs1883025 and rs2108622 was performed using the RT-PCR method. The best-corrected visual acuity (BCVA) and central retinal thickness (CRT) were measured before anti-VEGF therapy, then at three and six months during the therapy, using optical coherence tomography (OCT). The patients were grouped to responders and non-responders according to the changes in BCVA and CRT. Results: The T allele at rs1883025 was more frequent in non-responder eAMD patients compared to responder eAMD patients (41.7% vs. 21.1%; p = 0.009). The analysis of rs2108622 gene polymorphism did not reveal any differences in the distribution of C/C, C/T, and T/T genotypes between the eAMD group and the control group (56.35%, 39.78%, and 3.87% in the eAMD group and 53.33%, 39.05% and 7.62% in the control group, respectively, p = 0.286). The comparison of CRT and BCVA between the rs2108622 genotypes revealed statistically significant differences: CRT was thicker for the CC carriers than for those with CT and TT genotypes (p = 0.030). Conclusion: The rs1883025 T allele was found to play a more significant role in non-responder eAMD patients compared to responder eAMD patients. The rs2108622 genotypes revealed statistically significant differences: CRT was thicker for the CC carriers than for those with CT and TT genotypes.

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“…This association was between rs3773978 polymorphism of IL‐1RAcP and AAU, suggesting that this specific polymorphism can be suggested as a genetic risk marker for AAU [54]. Similarly, rs4624606 polymorphism was studied in AMD (Table 1) [55].…”

Section: Uveitismentioning

confidence: 99%

The roles of interleukin‐1 receptor accessory protein in certain inflammatory conditions

et al. 2022

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Interleukin‐1 receptor accessory protein (IL‐1RAcP) is a member of the immunoglobulin superfamily proteins consisting of soluble and membranous isoforms. IL‐1RAcP plays an essential role in the signaling of the IL‐1 family cytokines such as IL‐1, IL‐33 and IL‐36, as well as tyrosine kinases FLT3 and C‐Kit. IL‐1RAcP generally initiates inflammatory signaling pathway through the recruitment of signaling mediators, including MYD88 and IRAK. Chronic inflammation following prolonged signaling of cytokine receptors is a critical process in the pathogenesis of many inflammatory disorders, including autoimmunity, obesity, psoriasis, type 1 diabetes, endometriosis, preeclampsia and Alzheimer's disease. Recently IL‐1RAcP aberrant signaling has been considered to play a central role in the pathogenesis of these chronic inflammatory diseases. Targeting IL‐1RAcP signaling pathway that was recently considered in clinical trials related to malignancies also indicates its potential as therapeutic target for the inflammatory and autoimmune diseases. This review summarizes the molecular structure, components associated with IL‐1RAcP signaling pathways, and their involvement in the pathogenesis of different inflammatory diseases. We will also discuss the effect of IL‐1RAcP inhibition for treatment proposes.

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The Role of SNPs in IL1RL1 and IL1RAP Genes in Age-related Macular Degeneration Development and Treatment Efficacy

Cited by 5 publications

References 41 publications

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

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

ABCA1 rs1883025 and CYP4F2 rs2108622 Gene Polymorphism Association with Age-Related Macular Degeneration and Anti-VEGF Treatment

The roles of interleukin‐1 receptor accessory protein in certain inflammatory conditions

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