Cebatoriene Dzastina, Vilkeviciute Alvita, Gedvilaite Greta, Bruzaite Akvile, Kriauciuniene Loresa, Zaliuniene Dalia, Liutkeviciene Rasa
Medical Academy, Lithuanian University of Health Sciences, A. Mickeviciaus St. 9, LT-44307 Kaunas, Lithuania.
Neuroscience Institute, Medical Academy, Lithuanian University of Health Sciences, Eiveniu St. 2, LT-50161 Kaunas, Lithuania.
Biomedicines. 2024 Apr 24;12(5):948. doi: 10.3390/biomedicines12050948.
Age-related macular degeneration (AMD) is a major global health problem as it is the leading cause of irreversible loss of central vision in the aging population. Av-vascular endothelial growth factor (anti-VEGF) therapies have been shown to be effective, but they do not respond optimally to all patients.
This study investigates the genetic factors associated with susceptibility to AMD and response to treatment, focusing on key polymorphisms in the (rs1061170, rs1410996) and (rs2071559, rs1870377) genes and the association of CFH and KDR serum levels in patients with AMD.
A cohort of 255 patients with early AMD, 252 patients with exudative AMD, and 349 healthy controls underwent genotyping analysis, which revealed significant associations between CFH polymorphisms and the risk of exudative AMD. The rs1061170 CC genotype was associated with an increased risk of early AMD ( = 0.046). For exudative AMD, the rs1061170 TC + CC genotype increased odds ( < 0.001), while the rs1410996 GA + AA genotype decreased odds ( < 0.001). Haplotypes of SNPs were associated with decreased odds of AMD. In terms of response to treatment, none of the SNPs were associated with the response to anti-VEGF treatment. We also found that both early and exudative AMD patients had lower CFH serum levels compared to the control group ( = 0.038 and = 0.006, respectively). Exudative AMD patients with the CT genotype of rs1061170 had lower CFH serum levels compared to the control group ( = 0.035). Exudative AMD patients with the GG genotype of rs1410996 also had lower CFH serum levels compared to the control group ( = 0.021).
polymorphisms influence susceptibility to AMD but do not correlate with a response to anti-VEGF therapy. Further research is imperative to fully evaluate the developmental significance, treatment efficacy, and predictive role in influencing susceptibility to anti-VEGF therapy for KDR and CFH.
年龄相关性黄斑变性（AMD）是一个重大的全球健康问题，因为它是老年人群中心视力不可逆丧失的主要原因。抗血管内皮生长因子（抗VEGF）疗法已被证明是有效的，但并非对所有患者都能达到最佳效果。
本研究调查与AMD易感性及治疗反应相关的遗传因素，重点关注CFH基因（rs1061170、rs1410996）和KDR基因（rs2071559、rs1870377）中的关键单核苷酸多态性，以及AMD患者中CFH和KDR血清水平的关联。
对255例早期AMD患者、252例渗出性AMD患者和349例健康对照进行基因分型分析，结果显示CFH基因多态性与渗出性AMD风险之间存在显著关联。CFH基因rs1061170的CC基因型与早期AMD风险增加相关（P = 0.046）。对于渗出性AMD，CFH基因rs1061170的TC + CC基因型增加了患病几率（P < 0.001），而rs1410996的GA + AA基因型降低了患病几率（P < 0.001）。CFH基因单核苷酸多态性的单倍型与AMD患病几率降低相关。在治疗反应方面，没有一个单核苷酸多态性与抗VEGF治疗反应相关。我们还发现，与对照组相比，早期和渗出性AMD患者的CFH血清水平均较低（分别为P = 0.038和P = 0.006）。CFH基因rs1061170的CT基因型渗出性AMD患者的CFH血清水平低于对照组（P = 0.035）。CFH基因rs1410996的GG基因型渗出性AMD患者的CFH血清水平也低于对照组（P = 0.021）。
CFH基因多态性影响AMD易感性，但与抗VEGF治疗反应无关。必须进一步研究以全面评估KDR和CFH在影响抗VEGF治疗易感性方面的发育意义、治疗效果和预测作用。
