Macular telangiectasia type 2 genetic risk variants associated with clinical characteristics in the Slovenian cohort
4 affiliations
- 1Faculty of Medicine, Institute of Biochemistry and Molecular Genetics, Medical Centre for Molecular Biology University of Ljubljana Ljubljana Slovenia
- 2Faculty of Medicine, Institute of Biochemistry and Molecular Genetics University of Ljubljana Ljubljana Slovenia
- 3Faculty of Medicine University of Ljubljana Ljubljana Slovenia
- 4Eye Hospital University Medical Centre Ljubljana Ljubljana Slovenia
Abstract
Purpose: Early diagnosis of macular telangiectasia type 2 (MacTel) remains challenging, and the contribution of genetic variation to its clinical heterogeneity is unclear. This study investigated associations between MacTel risk variants and clinical characteristics in a Slovenian cohort.
Methods: In this case–control study, including 65 patients with MacTel and 73 healthy controls, participants underwent a complete ophthalmological examination and multimodal imaging. Clinical parameters included best‐corrected visual acuity (BCVA), retinal thickness, area of ellipsoid zone (EZ) break, retinal pigment epithelium (RPE) hyperplasia and neovascularization (NV). Ten MacTel risk variants were genotyped using TaqMan assays. A polygenic risk score (PRS) was calculated, and phenotype–phenotype and genotype–phenotype associations were evaluated using correlation and regression analyses.
Results: Visual acuity declined with progressive retinal changes, including a larger area of EZ break (ρ = 0.72), RPE hyperplasia (ρ = 0.49) and NV (ρ = 0.55; all p adj < 0.05). Two variants showed nominal differences in minor allele frequency between groups: rs36259 (CERS4) and rs146953046 (PHGDH), with the latter associated with higher odds of MacTel (OR = 3.51, p = 0.040). The rs11077850‐C allele (SNHG16) showed nominal associations with better BCVA (logMAR) (ρ = −0.33, p = 0.0066), a smaller area of EZ break (ρ = −0.27, p = 0.032) and lower odds of progressed disease (OR = 0.30, p = 0.011). These associations were attenuated after FDR correction. A PRS constructed from five MacTel risk variants, combined with age moderately discriminated patients from controls (AUC = 0.68).
Conclusion: MacTel risk variants are associated with clinically relevant functional and structural retinal changes. Integrating genetic information with multimodal imaging may support risk stratification and earlier recognition in selected patients.
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BibTeX
@article{kuncic2026macular,
title = {{Macular telangiectasia type 2 genetic risk variants associated with clinical characteristics in the Slovenian cohort}},
author = {Ajda Kunčič and Nataša Debeljak and Petra Hudler and Janez Smerkolj and Mojca Urbančič},
journal = {Acta Ophthalmologica},
year = {2026},
month = jul,
doi = {10.1111/aos.70197},
url = {https://doi.org/10.1111/aos.70197},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Macular telangiectasia type 2 genetic risk variants associated with clinical characteristics in the Slovenian cohort
AU - Ajda Kunčič
AU - Nataša Debeljak
AU - Petra Hudler
AU - Janez Smerkolj
AU - Mojca Urbančič
PY - 2026
DA - 2026/07/28
JO - Acta Ophthalmologica
DO - 10.1111/aos.70197
UR - https://doi.org/10.1111/aos.70197
AB - Purpose: Early diagnosis of macular telangiectasia type 2 (MacTel) remains challenging, and the contribution of genetic variation to its clinical heterogeneity is unclear. This study investigated associations between MacTel risk variants and clinical characteristics in a Slovenian cohort. Methods: In this case–control study, including 65 patients with MacTel and 73 healthy controls, participants underwent a complete ophthalmological examination and multimodal imaging. Clinical parameters included best‐corrected visual acuity (BCVA), retinal thickness, area of ellipsoid zone (EZ) break, retinal pigment epithelium (RPE) hyperplasia and neovascularization (NV). Ten MacTel risk variants were genotyped using TaqMan assays. A polygenic risk score (PRS) was calculated, and phenotype–phenotype and genotype–phenotype associations were evaluated using correlation and regression analyses. Results: Visual acuity declined with progressive retinal changes, including a larger area of EZ break (ρ = 0.72), RPE hyperplasia (ρ = 0.49) and NV (ρ = 0.55; all p adj < 0.05). Two variants showed nominal differences in minor allele frequency between groups: rs36259 (CERS4) and rs146953046 (PHGDH), with the latter associated with higher odds of MacTel (OR = 3.51, p = 0.040). The rs11077850‐C allele (SNHG16) showed nominal associations with better BCVA (logMAR) (ρ = −0.33, p = 0.0066), a smaller area of EZ break (ρ = −0.27, p = 0.032) and lower odds of progressed disease (OR = 0.30, p = 0.011). These associations were attenuated after FDR correction. A PRS constructed from five MacTel risk variants, combined with age moderately discriminated patients from controls (AUC = 0.68). Conclusion: MacTel risk variants are associated with clinically relevant functional and structural retinal changes. Integrating genetic information with multimodal imaging may support risk stratification and earlier recognition in selected patients.
SN - 1755-375X
SN - 1755-3768
ER -