Genetic associations in polypoidal choroidal vasculopathy: A systematic review and meta-analysis

PURPOSE To investigate the genetic associations of polypoidal choroidal vasculopathy (PCV), the genetic difference between PCV and age-related macular degeneration (AMD), and the genotype-phenotype correlation of PCV. METHODS A systematic review and meta-analysis were performed. Published articles about genetic associations of PCV identified from a literature search were reviewed. The following data from individual studies were extracted and analyzed: 1) comparison of genetic polymorphisms between PCV and controls; 2) comparison of genetic polymorphisms between PCV and AMD; and 3) comparison of phenotypes between different genotype groups. RESULTS A total of 33 articles fulfilled the inclusion criteria. With meta-analyses, variants in four genes were found to be significantly associated with PCV: LOC387715 rs10490924 (n=9, allelic odds ratio [OR]=2.27, p<0.00001), HTRA1 rs11200638 (n=4, OR=2.72, p<0.00001), CFH rs1061170 (n=4, OR=1.72, p<0.00001), CFH rs800292 (n=5, OR=2.10, p<0.00001), and C2 rs547154 (n=3, OR=0.56, p=0.01). LOC387715 rs10490924 was the only variant showing a significant difference between PCV and wet AMD (n=5, OR=0.66, p<0.00001). The risk genotypes of rs10490924 were associated with larger lesion size, greater chance of vitreous hemorrhage, and worse therapeutic response in PCV. CONCLUSIONS LOC387715 rs10490924 was associated with PCV and its clinical manifestations, and showed a discrepant distribution between PCV and AMD. Variants in HTRA1, CFH, and C2 were also associated with PCV.