The Association of Previously-Reported Genetic Markers with Clinical Phenotypes of Polypoidal Choroidal Vasculopathy

Abstract

Purpose : Genetic studies of polypoidal choroidal vasculopathy (PCV) have identified the association of some single nucleotide polymorphisms (SNPs) with PCV, but little is known about whether these SNPs are related to PCV clinical features. We performed this study to examine the association of 12 PCV-associated SNPs with PCV clinical phenotypes.

Methods : 69 PCV eyes of 69 patients were included. Genomic DNA was extracted from peripheral blood under standard procedures. Agilent SureSelect Human ALL Exon V6 was used to sequence the 12 SNPs previously reported to associate with PCV. Patients were classified into polypoidal choroidal neovascularization (CNV) and typical PCV based on whether feeder or draining vessels of polyps were visible in indocyanine green angiography (ICGA). Baseline sub-foveal choroidal thickness (SFCT), choroid maximum vascular diameter (MVD), choroidal vascular hyperpermeability (CVH) and greatest linear dimension (GLD) of entire leision determined with fluorescein angiography (FA) and ICGA were measured and compared between patients of different genotypes. Fisher’s exact test and Mann-Whitney U test were performed to compare categorical and continuous variables respectively. Values of P < 0.05 were considered statistically significant.

Results : ARMS2 rs2736911 was related to ICGA-based angiographic classification (P = 0.042). HTRA1 rs2293870 was related with greater SFCT after multiple linear regression (P = 0.043) and was a protective factor of PCV or AMD in the fellow eye (P = 0.040). C3 rs17030 was associated with smaller GLD (P = 0.033). CFH rs2274700 was related to smaller MVD (P = 0.043), and was a protective factor for CVH (P = 0.034).

Conclusions : Multiple PCV-associated SNPs were associated with PCV clinical phenotypes. The involvement of several synonymous SNPs calls for further research on the role of transcriptional alterations and trans-regulation of distant signaling pathways in PCV pathogenesis.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

 

SNP, single nucleotide polymorphism; PCV, polypoidal choroidal vasculopathy; OR, odds ratio; CNV, choroidal neovascularization; CVH, choroidal vascular hyperpermeability.

 

^* Only rs2293870 remained significantly associated with higher SFCT after multiple linear regression.
SNP, single nucleotide polymorphism; PCV, polypoidal choroidal vasculopathy; SFCT, sub-foveal choroidal thickness; MVD, maximum vascular diameter; GLD, greatest linear dimension.