Cui Jinglin, Lu Hang, Wang Suoxi, Li Zhuo, Song Xiande, Xiu Weiwei, Liu Boyang, Li Jiayao, Jin Chaoming, Zhao Anqi, Ding Hongyang, Sun Dawei, Jablonski Monica M, Lu Lu, Gu Weikuan, Yang Baofeng
Department of Ophthalmology, The First Hospital of Qiqihar City, Qiqihar, Heilongjiang, China.
Biomedical Sciences, University of Tennessee Health Science Center, Memphis, Tennessee, USA.
BMJ Open Ophthalmol. 2025 Apr 12;10(1):e001872. doi: 10.1136/bmjophth-2024-001872.
To compare the genetic characteristics of the normal control group to those of neovascular age-related macular degeneration (AMD) patients and to detect single-nucleotide polymorphisms (SNPs) related to the pathogenesis of neovascular AMD and the sensitivity to anti-VEGF drug, combercept.
This is a prospective case-controlled study. A total of 104 neovascular AMD patients were treated with combercept and 106 normal subjects were served as the control group. SNPs associated with neovascular AMD and disease susceptibility and drug sensitivity were analysed.
Significant differences existed between neovascular AMD patients and normal subjects among genotypes of the SNPs of two genes, ARMS2 (rs10490924 T) and HTRA 1 (rs11200638 A). The T alleles in rs1065489 of CFH and the rs2230205 of C3 significantly promoted neovascular AMD in males while having no significant effect in females. Six SNPs of five genes, including C3 (rs2250656 G), CFB (rs2072633 G), CFH (rs2274700 A, rs3766405 T), KDR (rs6828477 A) and FZD 4 (rs10898563 T), had significant impact in reducing neovascular AMD. Two SNPs of the CFH gene (rs2274700 A and rs3766405 T) and one SNP of the CFB gene, rs2072633 G, were statistically significantly associated with good response to combercept. Conversely, the other two SNPs of the CFH gene, rs1065489 T and rs3753396 G, and the rs7412 T of the APOE gene were associated with a relatively poor patient response to drug action. Two sets of SNPs of CFB have a combined positive effect on disease. The two SNPs of CFH (rs1065489 T and rs3753396 G) and the combination of the two SNPs of CFH and rs7412T of APOE have negative effects on the drug effectiveness.
These genotype differences facilitate the selection of individualised treatment options towards obtaining the most efficacious clinical treatment. These findings need to be validated by studies with different ethnic populations and/or larger samples.
比较正常对照组与新生血管性年龄相关性黄斑变性（AMD）患者的基因特征，检测与新生血管性AMD发病机制及抗VEGF药物康柏西普敏感性相关的单核苷酸多态性（SNP）。
这是一项前瞻性病例对照研究。共104例新生血管性AMD患者接受康柏西普治疗，106例正常受试者作为对照组。分析与新生血管性AMD、疾病易感性和药物敏感性相关的SNP。
在两个基因ARMS2（rs10490924 T）和HTRA1（rs11200638 A）的SNP基因型中，新生血管性AMD患者与正常受试者之间存在显著差异。CFH的rs1065489和C3的rs2230205中的T等位基因在男性中显著促进新生血管性AMD，而在女性中无显著影响。五个基因的六个SNP，包括C3（rs2250656 G）、CFB（rs2072633 G）、CFH（rs2274700 A、rs3766405 T）、KDR（rs6828477 A）和FZD 4（rs10898563 T），对降低新生血管性AMD有显著影响。CFH基因的两个SNP（rs2274700 A和rs3766405 T）以及CFB基因的一个SNP rs2072633 G与对康柏西普的良好反应在统计学上显著相关。相反，CFH基因的另外两个SNP，rs1065489 T和rs3753396 G，以及APOE基因的rs7412 T与患者对药物作用的反应相对较差相关。CFB的两组SNP对疾病有联合积极作用。CFH的两个SNP（rs1065489 T和rs3753396 G）以及CFH的两个SNP与APOE的rs7412T的组合对药物有效性有负面影响。
这些基因型差异有助于选择个体化治疗方案以获得最有效的临床治疗。这些发现需要通过不同种族人群和/或更大样本的研究来验证。
