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

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).

To identify genetic biomarkers that are potentially useful for genetic diagnosis of PCV and for differentiating PCV from nAMD.

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.

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.

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.