Department of Ophthalmology, University of Eastern Finland, 70211 Kuopio, Finland.
Department of Ophthalmology, Kuopio University Hospital, 70029 Kuopio, Finland.
Genes (Basel). 2020 Nov 6;11(11):1318. doi: 10.3390/genes11111318.
Age-related macular degeneration is an eye disease that is the main cause of legal blindness in the elderly in developed countries. Despite this, its pathogenesis is not completely known, and many genetic, epigenetic, environmental and lifestyle factors may be involved. Vision loss in age-related macular degeneration (AMD) is usually consequence of the occurrence of its wet (neovascular) form that is targeted in the clinic by anti-VEGF (vascular endothelial growth factor) treatment. The wet form of AMD is associated with the accumulation of cellular waste in the retinal pigment epithelium, which is removed by autophagy and the proteosomal degradation system. In the present work, we searched for the association between genotypes and alleles of single nucleotide polymorphisms (SNPs) of autophagy-related genes and wet AMD occurrence in a cohort of Finnish patients undergoing anti-VEGF therapy and controls. Additionally, the correlation between treatment efficacy and genotypes was investigated. Overall, 225 wet AMD patients and 161 controls were enrolled in this study. Ten SNPs (rs2295080, rs11121704, rs1057079, rs1064261, rs573775, rs11246867, rs3088051, rs10902469, rs73105013, rs10277) in the (Mechanistic Target of Rapamycin), (Autophagy Related 5), (Unc-51-Like Autophagy Activating Kinase 1), (Microtubule Associated Protein 1 Light Chain 3 α), (Sequestosome 1) were analyzed with RT-PCR-based genotyping. The genotype/alleles rs2295080-G, rs11121704-C, rs1057079-C and rs73105013-T associated with an increased, whereas rs2295080-TT, rs2295080-T, rs11121704-TT, rs1057079-TT, rs1057079-T, rs573775-AA and rs73105013-C with a decreased occurrence of wet AMD. In addition, the rs2295080-GG, rs2295080-GT, rs1057079-TT, rs11246867-AG, rs3088051-CC and rs10277-CC genotypes were a positively correlated cumulative number of anti-VEGF injections in 2 years. Therefore, variability in autophagy genes may have an impact on the risk of wet AMD occurrence and the efficacy of anti-VEGF treatment.
年龄相关性黄斑变性是一种眼部疾病，是发达国家老年人失明的主要原因。尽管如此，其发病机制尚不完全清楚，许多遗传、表观遗传、环境和生活方式因素可能与之相关。年龄相关性黄斑变性（AMD）导致的视力丧失通常是其湿性（新生血管）形式的结果，临床上通过抗血管内皮生长因子（VEGF）治疗来靶向治疗这种形式。AMD 的湿性形式与视网膜色素上皮细胞中细胞废物的积累有关，这些废物通过自噬和蛋白酶体降解系统来清除。在本工作中，我们在接受抗 VEGF 治疗的芬兰患者队列和对照组中，搜索了与自噬相关基因单核苷酸多态性（SNP）的基因型和等位基因与湿性 AMD 发生之间的关联。此外，还研究了治疗效果与基因型之间的相关性。总体而言，本研究纳入了 225 名湿性 AMD 患者和 161 名对照者。通过 RT-PCR 基于基因分型，对 （Mechanistic Target of Rapamycin）、 （Autophagy Related 5）、 （Unc-51-Like Autophagy Activating Kinase 1）、 （Microtubule Associated Protein 1 Light Chain 3α）、 （Sequestosome 1）中的 10 个 SNP（rs2295080、rs11121704、rs1057079、rs1064261、rs573775、rs11246867、rs3088051、rs10902469、rs73105013、rs102777）进行了分析。基因型/等位基因 rs2295080-G、rs11121704-C、rs1057079-C 与湿性 AMD 发生率增加相关，而 rs2295080-TT、rs2295080-T、rs11121704-TT、rs1057079-TT、rs1057079-T、rs573775-AA 和 rs73105013-C 与湿性 AMD 发生率降低相关。此外，rs2295080-GG、rs2295080-GT、rs1057079-TT、rs11246867-AG、rs3088051-CC 和 rs10277-CC 基因型与 2 年内抗 VEGF 注射的累积次数呈正相关。因此，自噬基因的多态性可能对湿性 AMD 发生的风险和抗 VEGF 治疗的效果有影响。
