Neuroscience Institute, Lithuanian University of Health Sciences, Medical Academy, Kaunas, Lithuania
Lithuanian University of Health Sciences, Medical Academy, Kaunas, Lithuania.
In Vivo. 2020 Sep-Oct;34(5):2443-2451. doi: 10.21873/invivo.12059.
Age-related macular degeneration (AMD) affects the central part of the retina and causes blindness. In developed countries, AMD occurs in people over 50 years old. Important factors for AMD pathogenesis are an immune response, inflammation, and genetic factors. This study aimed to determine the impact of IL1RL1 rs1041973 and IL1RAP rs4624606 single nucleotide polymorphisms (SNPs) on the occurrence of AMD and the outcome of treatment with aflibercept and bevacizumab.
563 patients with AMD and 281 healthy candidates were evaluated. Patients with exudative AMD were treated with intravitreal bevacizumab and aflibercept and, after 6 months based on the changes in best-corrected visual acuity and central macular thickness, were classified as 'responders' or 'poor-responders'. Genotyping of IL1RL1 rs1041973 and IL1RAP rs4624606 was accomplished using real-time PCR. Age was compared using the Mann-Whitney U-test. Categorical data (gender, genotype, and allele distributions) compared between groups using the χ test or the Fisher's exact test. Associations of gene polymorphisms were calculated using logistic regression analysis with adjustment for age in exudative and atrophic AMD analysis. An adjusted significance threshold for multiple comparisons α=0.025 was applied.
Statistically significant differences in the distribution of IL1RAP rs4624606 genotypes (TT, TA and AA) were found between males with atrophic AMD and controls: 50%, 42.9% and 7.1% vs. 69.7%, 30.3% and 0%, respectively, p=0.015. Moreover, we found that 'responders' had a significantly better best-corrected visual acuity than 'poor-responders' before treatment (p=0.032). The central macular thickness was significantly lower in exudative AMD patients with IL1RL1 rs1041973 AA genotype than in wild type and heterozygous (CC+CA) genotype carriers before treatment (p=0.017).
IL1RAP rs4624606 may be associated with atrophic AMD in males while IL1RL1 rs1041973 may play a protective role against macular thickening in exudative AMD patients.
年龄相关性黄斑变性（AMD）影响视网膜中央部分，导致失明。在发达国家，AMD 发生在 50 岁以上的人群中。AMD 发病机制的重要因素是免疫反应、炎症和遗传因素。本研究旨在确定 IL1RL1 rs1041973 和 IL1RAP rs4624606 单核苷酸多态性（SNPs）对 AMD 发生的影响，以及对阿柏西普和贝伐单抗治疗效果的影响。
评估了 563 名 AMD 患者和 281 名健康对照者。患有渗出性 AMD 的患者接受了玻璃体内贝伐单抗和阿柏西普治疗，并根据最佳矫正视力和中心黄斑厚度的变化，在 6 个月后将其分类为“应答者”或“无应答者”。使用实时 PCR 完成 IL1RL1 rs1041973 和 IL1RAP rs4624606 的基因分型。使用 Mann-Whitney U 检验比较年龄。使用 χ 检验或 Fisher 确切检验比较组间的分类数据（性别、基因型和等位基因分布）。使用 logistic 回归分析计算基因多态性与渗出性和萎缩性 AMD 分析中年龄调整的关联。应用调整后的多重比较显著性阈值 α=0.025。
在男性萎缩性 AMD 患者与对照组之间，IL1RAP rs4624606 基因型（TT、TA 和 AA）的分布存在统计学显著差异：50%、42.9%和 7.1%，分别为 69.7%、30.3%和 0%，p=0.015。此外，我们发现治疗前“应答者”的最佳矫正视力明显好于“无应答者”（p=0.032）。在渗出性 AMD 患者中，与野生型和杂合型（CC+CA）携带者相比，IL1RL1 rs1041973 AA 基因型患者的中央黄斑厚度在治疗前明显较低（p=0.017）。
IL1RAP rs4624606 可能与男性萎缩性 AMD 相关，而 IL1RL1 rs1041973 可能在渗出性 AMD 患者中发挥对黄斑增厚的保护作用。
