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Abstract：
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 (RAD51B rs8017304, rs2588809; TRIB1 rs6987702, rs4351379; COL8A1 rs13095226; COL10A1 rs1064583; IL-9 rs1859430, rs2069870, rs11741137, rs2069885, rs2069884; IL-10 rs1800871, rs1800872, rs1800896; VEGFA 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 RAD51B rs8017304 heterozygous and homozygous minor allele carriers had increased CMT before treatment compared to wild-type genotype carriers (p = 0.004). Additionally, TRIB1 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 (p = 0.030). IL-9 rs1859430, rs2069870, and rs2069884 heterozygous and homozygous minor allele carriers had worse BCVA before treatment than wild-type genotype carriers (p = 0.018, p = 0.012, p = 0.041, respectively). Conversely, IL-9 rs2069885 heterozygous and homozygous minor allele carriers showed greater improvement in BCVA after 6 months compared to wild-type genotype carriers (p = 0.032). Furthermore, VEGFA 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 (p = 0.003, p = 0.022, respectively), with these carriers also exhibiting higher CMT after 6 months of anti-VEGF treatment (p = 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 RAD51B rs8017304, TRIB1 rs4351379, IL-9 rs1859430, rs2069870, rs2069884, rs2069885, and VEGFA rs699947, and parameters related to the efficacy of exudative AMD treatment, such as BCVA and CMT.
摘要：
年龄相关性黄斑变性（AMD）是一种进行性神经退行性疾病，导致视力丧失和最终失明。由于脉络膜新生血管形成和局部水肿，渗出性AMD的风险增加。靶向VEGF途径的疗法旨在解决治疗有效性的这种机制。我们的研究旨在评估特定遗传变异之间的关联（RAD51Brs8017304，rs2588809;TRIB1rs6987702，rs4351379;COL8A1rs13095226;COL10A1rs1064583;IL-9rs1859430，rs2069870，rs1137，rs20r00rexAMD治疗，r18rs88我们招募了119名渗出性AMD患者，根据他们对抗VEGF治疗的反应分为应答者或非应答者。统计分析表明，与野生型基因型携带者相比，RAD51Brs8017304杂合和纯合次要等位基因携带者在治疗前的CMT增加（p=0.004）。此外,TRIB1rs4351379杂合和纯合次要等位基因携带者在治疗6个月后表现出比野生型基因型携带者更大的中央黄斑厚度（CMT）下降（p=0.030）。IL-9rs1859430、rs2069870和rs2069884杂合和纯合次要等位基因携带者治疗前的BCVA比野生型基因型携带者差(分别为p=0.018、p=0.012、p=0.041)。相反，与野生型基因型携带者相比，IL-9rs2069885杂合和纯合次要等位基因携带者在6个月后在BCVA中显示出更大的改善（p=0.032）。此外，VEGFArs699947杂合子和纯合子次要等位基因携带者在治疗前和治疗3个月和6个月后的BCVA均优于野生型基因型携带者（分别为p=0.003，p=0.022），这些载体在抗VEGF治疗6个月后也表现出更高的CMT(p=0.032)。在多重比较的这种严格校正下，并非所有结果都具有统计学意义。血清IL-10、VEGF-A、无应答者和应答者之间的VEGF-R2/KDR没有产生统计学上的显著差异。我们的研究确定了遗传变异之间的显著关联，包括RAD51Brs8017304，TRIB1rs4351379，IL-9rs1859430，rs2069870，rs2069884，rs2069885和VEGFArs699947，以及与渗出性AMD治疗疗效相关的参数，如BCVA和CMT。
