Neuroscience Institute, Lithuanian University of Health Sciences, Medical Academy, Eiveniu St. 2, LT-50161 Kaunas, Lithuania.
Medical Academy, Lithuanian University of Health Sciences, A. Mickeviciaus St. 9, LT-44307 Kaunas, Lithuania.
Int J Mol Sci. 2024 Jun 22;25(13):6859. doi: 10.3390/ijms25136859.
Age-related macular degeneration (AMD) is a progressive neurodegenerative condition leading to vision loss and eventual blindness, with exudative AMD posing a heightened risk due to choroidal neovascularization and localized edema. Therapies targeting the VEGF pathway aim to address this mechanism for treatment effectiveness. Our study aimed to evaluate associations between specific genetic variants ( rs8017304, rs2588809; rs6987702, rs4351379; rs13095226; rs1064583; rs1859430, rs2069870, rs11741137, rs2069885, rs2069884; rs1800871, rs1800872, rs1800896; rs1570360, rs699947, rs3025033, rs2146323) and the response to anti-VEGF treatment for exudative AMD. We enrolled 119 patients with exudative AMD categorized as responders or non-responders based on their response to anti-VEGF treatment. Statistical analysis revealed that rs8017304 heterozygous and homozygous minor allele carriers had increased CMT before treatment compared to wild-type genotype carriers ( = 0.004). Additionally, rs4351379 heterozygous and homozygous minor allele carriers exhibited a greater decrease in central macular thickness (CMT) after 6 months of treatment than wild-type genotype carriers ( = 0.030). rs1859430, rs2069870, and rs2069884 heterozygous and homozygous minor allele carriers had worse BCVA before treatment than wild-type genotype carriers ( = 0.018, = 0.012, = 0.041, respectively). Conversely, rs2069885 heterozygous and homozygous minor allele carriers showed greater improvement in BCVA after 6 months compared to wild-type genotype carriers ( = 0.032). Furthermore, rs699947 heterozygous and homozygous minor allele carriers had better BCVA before treatment and after 3 and 6 months of treatment than wild-type genotype carriers ( = 0.003, = 0.022, respectively), with these carriers also exhibiting higher CMT after 6 months of anti-VEGF treatment ( = 0.032). Not all results remained statistically significant under this stringent correction for multiple comparisons. The comparisons of the serum concentrations of IL-10, VEGF-A, and VEGF-R2/KDR between non-responders and responders did not yield statistically significant differences. Our study identified significant associations between genetic variants, including rs8017304, rs4351379, rs1859430, rs2069870, rs2069884, rs2069885, and rs699947, and parameters related to the efficacy of exudative AMD treatment, such as BCVA and CMT.
年龄相关性黄斑变性 (AMD) 是一种进行性神经退行性疾病，可导致视力丧失和最终失明，渗出性 AMD 由于脉络膜新生血管形成和局部水肿而存在更高的风险。针对 VEGF 途径的治疗旨在针对该机制进行治疗效果。我们的研究旨在评估特定遗传变异（rs8017304、rs2588809；rs6987702、rs4351379；rs13095226；rs1064583；rs1859430、rs2069870、rs11741137、rs2069885、rs2069884；rs1800871、rs1800872、rs1800896；rs1570360、rs699947、rs3025033、rs2146323）与渗出性 AMD 对抗 VEGF 治疗的反应之间的关联。我们招募了 119 名渗出性 AMD 患者，根据他们对抗 VEGF 治疗的反应分为反应者和非反应者。统计分析显示，与野生型基因型携带者相比，rs8017304 杂合和纯合的次要等位基因携带者在治疗前的 CMT 更高（=0.004）。此外，与野生型基因型携带者相比，rs4351379 杂合和纯合的次要等位基因携带者在治疗 6 个月后中央黄斑厚度（CMT）下降更大（=0.030）。rs1859430、rs2069870 和 rs2069884 杂合和纯合的次要等位基因携带者在治疗前的 BCVA 比野生型基因型携带者差（=0.018、=0.012、=0.041，分别）。相反，rs2069885 杂合和纯合的次要等位基因携带者在治疗 6 个月后 BCVA 改善大于野生型基因型携带者（=0.032）。此外，rs699947 杂合和纯合的次要等位基因携带者在治疗前和治疗 3 个月和 6 个月后 BCVA 更好（=0.003、=0.022，分别），这些携带者在抗 VEGF 治疗 6 个月后 CMT 也更高（=0.032）。并非所有结果在这种严格的多重比较校正下仍具有统计学意义。非反应者和反应者之间血清白细胞介素 10、血管内皮生长因子-A 和血管内皮生长因子受体 2/激酶（VEGF-R2/KDR）浓度的比较没有产生统计学上的显著差异。我们的研究确定了 rs8017304、rs4351379、rs1859430、rs2069870、rs2069884、rs2069885 和 rs699947 等遗传变异与渗出性 AMD 治疗效果相关的参数（如 BCVA 和 CMT）之间存在显著关联。
