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. 2025 Aug;53(6):660-667.
doi: 10.1111/ceo.14539. Epub 2025 Apr 15.

Genetic Association of Primary Angle-Closure Glaucoma and Disease Progression

Yu Jing Liang  1   2 , Anni Ling  1   2 , Poemen P Chan  1   2   3 , Jason C Yam  1   2   3 , Chi Pui Pang  1   2 , Clement C Tham  1   2   3   4 , Li Jia Chen  1   2   3   4
Affiliations

Genetic Association of Primary Angle-Closure Glaucoma and Disease Progression

Yu Jing Liang et al. Clin Exp Ophthalmol. 2025 Aug.

Abstract

Background: To investigate single-nucleotide polymorphisms (SNPs) reported in the largest up-to-date systematic review and meta-analysis on primary angle-closure disease (PACD), on their associations with primary angle-closure glaucoma (PACG) and disease progression.

Methods: This study involved a case-control design for PACG risk and a case-only design for PACG progression risk, including 628 PACG patients and 564 controls for disease association and 386 PACG patients with up to 10-year follow-up for PACG progression analysis. Associations of 17 SNPs in 15 genes with PACG were analysed using logistic regression. Sex-stratified association analysis was performed, followed by the Breslow-Day test. Genetic risk for PACG progression was evaluated using logistic regression. Bonferroni correction of p values was adopted for multiple comparisons.

Results: LOXL1 rs3825942 (G153D; p = 0.0026; OR = 0.65) was significantly associated with PACG, while ABCC5 rs1401999 showed a nominal association (p = 0.023; OR = 1.32). ABCA1 rs2422493 was significantly associated with PACG in females (p = 0.0016; OR = 0.70) but not in males (p = 0.95; OR = 0.99); and the Breslow-Day Test (p = 0.046) suggested a sex-specific association in females. VAV3 rs6689476 showed nominal associations with PACG progression at 3-year (p = 0.045; OR = 2.86), 5-year (p = 0.037; OR = 2.84) and 10-year follow-ups (p = 0.03; OR = 2.74), but the p values could not withstand Bonferroni correction.

Conclusion: This study demonstrated a role of LOXL1 in PACG and a sex-specific effect of ABCA1 in the Hong Kong Chinese population while suggesting a potential role of VAV3 in PACG progression, which has yet to be further confirmed.

Keywords: candidate gene investigation; disease progression; genetics; primary angle‐closure glaucoma.

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Conflict of interest statement

The authors declare no conflicts of interest.

References

    1. Jonas J. B., Aung T., Bourne R. R., Bron A. M., Ritch R., and Panda‐Jonas S., “Glaucoma,” Lancet 390, no. 10108 (November 2017): 2183–2193. - PubMed
    1. Zhang N., Wang J., Chen B., Li Y., and Jiang B., “Prevalence of Primary Angle Closure Glaucoma in the Last 20 Years: A Meta‐Analysis and Systematic Review,” Frontiers in Medicine 7 (2020): 624179. - PMC - PubMed
    1. Tham Y. C., Li X., Wong T. Y., Quigley H. A., Aung T., and Cheng C. Y., “Global Prevalence of Glaucoma and Projections of Glaucoma Burden Through 2040: A Systematic Review and Meta‐Analysis,” Ophthalmology 121, no. 11 (2014): 2081–2090. - PubMed
    1. Ahram D. F., Alward W. L., and Kuehn M. H., “The Genetic Mechanisms of Primary Angle Closure Glaucoma,” Eye (London, England) 29, no. 10 (2015): 1251–1259. - PMC - PubMed
    1. Vithana E. N., Khor C. C., Qiao C., et al., “Genome‐Wide Association Analyses Identify Three New Susceptibility Loci for Primary Angle Closure Glaucoma,” Nature Genetics 44, no. 10 (October 2012): 1142–1146. - PMC - PubMed

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