Abstract
OBJECTIVE: 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. METHOD: 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. RESULTS: 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. CONCLUSIONS: 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.