Genetic Association of Primary Angle-Closure Glaucoma and Disease Progression.

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.