This study was the first to identify a single nucleotide polymorphism (rs56257842 at TEX29 - LINC02337) associated with myopic MNV in patients with high myopia, expanding our knowledge of the condition’s pathogenesis. Photo: Julie Poteet, OD. Click image to enlarge.

Macular neovascularization (MNV) is a key driver in the pathogenesis of both myopic MNV (mMNV) and age-related macular degeneration (AMD). Since the development of MNV associated with AMD is believed to be largely due to genetic factors, a team of researchers recently performed a meta-analysis on three genome-wide association analyses (GWAS) aiming to achieve two primary goals: first, identify the susceptibility loci for myopic mNV in patients with high myopia, and second, compare these loci with AMD susceptibility genes that have previously been shown to share genetic susceptibility between mMNV and macular degeneration.

Included in the analysis were 2,783 high myopes—608 with mMNV and 2,175 without, the latter acting as the control group. Data was adjusted for age, sex, axial length and the first to third principal components.

The meta-analysis identified rs56257842 at TEX29 - LINC02337 as a novel susceptibility single nucleotide polymorphism (SNP) for mMNV, with an odds ratio of 0.62. That SNP was consistently associated with mMNV in all three datasets.

The results also revealed that “the degree of binding of three transcription factors—EGR1, ZNF740, and ZBTB33—to this region was altered by this SNP genotype, suggesting their potential involvement in mMNV development,” the authors of the study explained in their paper, published last week in Ophthalmology Retina.

Furthermore, the analysis demonstrated that mMNV had a shared genetic susceptibility to AMD. “When we examined the associations of AMD susceptibility loci, rs12720922 at cholesteryl ester transfer protein showed a statistically significant association with mMNV,” the study authors wrote.

These findings have several implications for clinical research and deepening our understanding of mMNV pathogenesis. The authors noted that to their knowledge, this SNP (rs56257842 at TEX29 - LINC02337) is the first robust susceptibility SNP for mMNV to be documented.

“In conclusion,” they wrote, “we report the results of a genome-wide meta-analysis on mMNV development in patients with high myopia and the subsequent analyses offer important insights into the molecular biology of mMNV, providing potential therapeutic targets for mMNV. Further genetic studies will reveal the pathogenesis of mMNV in patients with high myopia.”