Genetics
Meta-analysis links CETP rs3764261 variant to higher age-related macular degeneration risk across ethnicities (Sci Rep 2015)
Original title: CETP/LPL/LIPC gene polymorphisms and susceptibility to age-related macular degeneration
This meta-analysis examined whether polymorphisms in three HDL-related genes, CETP, LIPC, and LPL, are associated with age-related macular degeneration (AMD) risk. The CETP rs3764261 variant was significantly associated with increased AMD risk (odds ratio 1.13, 95% CI, 1.05-1.21, P < 0.001), and the LIPC rs10468017 variant with significantly decreased risk (odds ratio 0.81, 95% CI, 0.76-0.86, P < 0.001), while the LPL rs12678919 variant showed no significant association (odds ratio 1.01, 95% CI, 0.92-1.10, P = 0.17). After adjusting for the complement factor H gene, both CETP and LPL conferred significantly increased AMD risk (CETP odds ratio 1.17, 95% CI, 1.08-1.26, P < 0.001; LPL odds ratio 1.11, 95% CI, 1.01-1.22, P = 0.02). Subgroup analysis found the CETP association held in both Americans (odds ratio 1.12, 95% CI, 1.02-1.23, P = 0.01) and Europeans (odds ratio 1.10, 95% CI, 1.01-1.19, P = 0.011), pointing to interactions between the complement and lipid metabolism pathways in AMD risk.
Original abstract
Three high-density lipoprotein (HDL)-related loci have been reported to be associated with age-related macular degeneration (AMD), but the results were inconsistent. In this study, the cholesteryl ester transfer protein (CETP) rs3764261 variant was significantly associated with an increased risk of AMD (odds ratio [OR] = 1.13, 95% confidence interval [CI]: 1.05-1.21, P < 0.001), and the hepatic lipase (LIPC) rs10468017 variant was associated with a significantly decreased risk of AMD (OR = 0.81, CI: 0.76-0.86, P < 0.001). Individuals carrying the lipoprotein lipase (LPL) rs12678919 polymorphism (A → G) had no significant change in the risk of developing AMD (OR = 1.01, CI: 0.92-1.10, P = 0.17). After adjusting for the complement factor H (CFH) gene, both CETP and LPL conferred a significantly increased AMD risk (ORCETP = 1.17, CI: 1.08-1.26, P < 0.001; ORLPL = 1.11, CI: 1.01-1.22, P = 0.02). Subgroup analysis based on ethnicity revealed a significant association between the CETP variant and AMD in both Americans (OR = 1.12, CI: 1.02-1.23, P = 0.01) and Europeans (OR = 1.10, CI: 1.01-1.19, P = 0.011). This meta-analysis revealed that both CETP rs3764261 and LIPC rs10468017 polymorphisms were significantly associated with AMD risk. After adjustment for the CFH gene, CETP/LPL conferred a significantly increased susceptibility to the disease, indicating potential interactions among genes in the complement system and the lipid metabolism pathway.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.