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.
Highlights
Three high-density lipoprotein (HDL)-related loci have been reported to be associated with agerelated macular degeneration (AMD), but the results were inconsistent
The present meta-analysis showed that the cholesteryl ester transfer protein (CETP) rs3764261 variant was associated with an increased risk of Age-related macular degeneration (AMD), and the LIPC rs10468017 variant could significantly reduce the susceptibility to AMD
Since 2010, several unknown genes associated with AMD have been identified by large-scale genome-wide association study (GWAS) investigations in the high-density lipoprotein cholesterol (HDL) pathway, whereas all previous genetic variants identified from candidate gene testing were mainly found in the complement factor pathway[9,10]
Summary
In all cases and control subjects, minor A-allele frequencies ranged from 0.32 to 0.37 for Americans, from 0.17 to 0.20 for Asians, and from 0.29 to 0.33 for Europeans. All included studies had case-control designs, and eleven of these studies were GWAS. The genotype frequency was in HWE in the controls for all included studies (P > 0 .05 for all), except for four studies that did not report the available data. Among the 11 included studies of the LPL rs12678919 polymorphism, seven studies were carried out in Caucasians, and four were performed in Asians. The average age of subjects ranged from 64.0 years to 81.2 years for cases and from 64.0 years to 77.4 years for controls. Nine studies adjusted for the CFH gene. Three studies adjusted for the CFH gene, whereas the others did not
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