Association of Genetic Variants with Polypoidal Choroidal Vasculopathy: A Systematic Review and Updated Meta-analysis.

Topic A systematic review and meta-analysis of the genetic association with polypoidal choroidal vasculopathy (PCV) and the genetic difference between PCV and neovascular age-related macular degeneration (nAMD). Clinical Relevance To identify genetic biomarkers that are potentially useful for genetic diagnosis of PCV and for differentiating PCV from nAMD. Methods We performed a literature search in EMBASE, PubMed, Web of Science, and the Chinese Biomedical Database for PCV genetic studies published before February 6, 2015. We then conducted a meta-analysis of all polymorphisms that had sufficient genotype/allele data reported in ≥2 studies and estimated the summary odds ratio (OR) and 95% confidence intervals (CIs) for PCV. We also compared the association profiles between PCV and nAMD, and performed a sensitivity analysis. Results A total of 66 studies were included in the meta-analysis, involving 56 polymorphisms in 19 genes/loci. In total, 31 polymorphisms in 10 genes/loci ( age-related maculopathy susceptibility 2 [ ARMS2 ], high-temperature requirement factor A1 [ HTRA1 ], complement factor H [ CFH ], complement component 2 [ C2 ], CFB , RDBP , SKIV2L , CETP , 8p21, and 4q12) were significantly associated with PCV. Another 25 polymorphisms in 13 genes ( ARMS2 , HTRA1 , C2 , CFB , ELN , LIPC , LPL , ABCA1 , VEGF-A , TLR3 , LOXL1 , SERPING1, and PEDF ) had no significant association. Twelve polymorphisms at the ARMS2-HTRA1 locus showed significant differences between PCV and nAMD. The sensitivity analysis validated the significance of our analysis. Conclusions This study revealed 31 polymorphisms in 10 genes/loci that contribute to PCV susceptibility. Among them, ARMS2-HTRA1 also showed allelic diversity between PCV and nAMD. Our results confirm the gene variants that could affect the phenotypic expressions of PCV and nAMD. [ABSTRACT FROM AUTHOR]