Genetic Factors For Choroidal Neovascularization Associated With High Myopia

Abstract

Purpose: : High myopia is defined by a refractive error greater than - 6 diopters (D) and is frequently associated with an increased risk of choroidal neovascularization (CNV). Exudative age-related macular degeneration (AMD), a degenerative retinal disease also characterized by a neovascular process, shares very similar phenotypic characteristics with CNV. Several genes are known to be associated with AMD, and the aim of this study was to investigate if these genes are also related to myopic CNV.

Methods: : We conducted a case-control study including 71 cases of myopic CNV and 196 myopic controls without CNV. Diagnosis of myopic CNV was confirmed by fluorescein angiography and spectral domain-OCT (HRA2, Spectralis). The study population included Caucasian patients and controls from Creteil (France), Toulouse (France) and Boston (MA, USA). A total of 29 SNPs in 15 candidate genes previously associated with AMD were selected and genotyped using Applied Biosystem (ABI) BioTrove OpenArray. Quality control, allele frequency estimation and tests for association were performed for each SNP using PLINK 1.07. SNPs were further tested for associations with CNV controlling for age, gender and degree of myopia using a multivariate logistic regression model. P values were corrected for multiple testing using the max(T) procedure (10,000 permutations) in PLINK.

Results: : In the univariate analysis, a polymorphism (rs10033900) located in the CFI gene (P = 0.0007, corrected P=0.028) was associated with myopic CNV. After adjustment for age, gender and degree of myopia, the rs10033900 SNP in CFI (P = 0.0017, corrected P = 0.045) remained associated with myopic CNV.

Conclusions: : The rs10033900 SNP, which is located in a gene linked with an inflammatory pathway, was associated with myopic CNV in our study. Further studies are needed to confirm a possible underlying role of inflammation in the pathophysiology of myopic CNV, as observed in AMD.

Keywords: choroid: neovascularization • genetics • myopia