Genetics
CETP rs3764261 T allele, a known atherosclerosis-protective variant, is linked to protection against eye inflammation after brolucizumab (Genes 2025)
Original title: Genetic Factors Associated with Intraocular Inflammation After Brolucizumab Administration in Patients with Exudative Age-Related Macular Degeneration
This study examined whether AMD-associated genetic variants are linked to intraocular inflammation (IOI) after intravitreal brolucizumab treatment in 206 eyes with exudative age-related macular degeneration, genotyping seven variants including CETP rs3764261 by TaqMan technology. Of the 206 patients, 21 eyes (10.2%) developed IOI, 4 severe (including retinal vasculitis or vascular occlusion) and 17 mild. The CETP T allele frequency was significantly lower in patients who developed IOI than in those who did not (9.5% versus 23.5%, p=0.036), and this association remained significant after adjusting for confounders (p=0.028, 95% CI 0.098-0.88). The authors conclude the CETP T allele, known as an AMD risk allele and an atherosclerosis-protective allele, may also protect against intraocular inflammation after brolucizumab administration.
Original abstract
Purpose: We aimed to investigate whether genetic variants susceptible to age-related macular degeneration (AMD) are associated with intraocular inflammation after brolucizumab administration in eyes that have exudative AMD. Methods: A total of 206 eyes from 206 patients (156 men/50 women, 74.0 ± 8.4 years; treatment-naïve, 128 [62.1%]; switching, 78 [37.9%]) were included in this study. All patients were treated with intravitreal brolucizumab at least once. The genotyping of ARMS2 A69S (rs10490924), CFH I62V (rs800292), CFH (rs1329428), SKIV2L (rs429608), C3 (rs2241394), cholesteryl ester transfer protein (CETP) (rs3764261), and ADAMTS9 (rs6795375) was performed using TaqMan technology. Results: Out of the 206 patients who were included, 21 eyes from 21 patients (10.2%) exhibited intraocular inflammation (IOI). Four (19.0%) exhibited severe IOI, including retinal vasculitis and/or retinal vascular occlusion, and 17 (81.0%) showed mild IOI. The frequency of the T allele of the CETP gene was significantly lower in patients who developed IOI compared to patients who did not develop IOI (T allele frequency: 9.5% vs. 23.5%, p = 0.036). After adjusting for confounding factors, the T allele remained significantly associated with protection against IOI (p = 0.028, 95% confidence interval: 0.098-0.88). Conclusions: The T allele of the CETP gene, a risk allele for AMD and the protective allele for atherosclerosis, may be associated with protection against IOI after brolucizumab administration in eyes that have exudative AMD.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.