Abstract
Purpose :
A locus at CACNA1A was identified as a genetic risk factor for exfoliation glaucoma (XFG); however, the biological mechanisms underlying the association are unknown. CACNA1A codes for the alpha 1A subunit of the type P/Q voltage-dependent calcium channel, which can be affected by antihypertensive drugs. We evaluated whether the relation between the top CACNA1A locus SNP and XFG is modified by hypertension.
Methods :
A total of 32,972 participants of the Nurses’ Health Study (1980–2018), the Health Professionals Follow-up Study (1986–2018), and the Nurses’ Health Study II (1991–2019) were followed biennially. Eligible subjects were 40+ years old, free of glaucoma, reported eye exams, and had genotype data for rs4926244 (T /C). Incident exfoliation glaucoma / glaucoma suspect (XFG/XFGS) cases were confirmed using medical records; self-reported information on physician-diagnosed hypertension was used. We used per-eye Cox proportional hazards models, accounting for inter-eye correlations, to estimate multivariable-adjusted relative risks (MVRRs), 95% confidence intervals (CIs) and used Wald tests of SNP x hypertension history to test for interactions.
Results :
During 1,244,137 eye-years of follow-up, 142 eyes with XFG/XFGS were documented. We confirmed a higher association with each minor allele [C) of rs4926244 (MVRR per C allele=1.76 (95% CI=1.00-3.12)), while hypertension was not significantly associated (MVRR=1.38 (95% CI=0.62-2.83)). We observed a significant interaction between hypertension and rs4926244 [C] (p-interaction = 0.002). Compared to non-carriers of the minor allele without hypertension (47% of eye-year-time), the non-carriers with hypertension (23%) had a significantly elevated risk (MVRR=3.02 (95% CI=1.38-6.58)) while carriers with hypertension (10%) did not (MVRR=0.58 (95% CI=0.11-3.10)).
Conclusions :
The presence of hypertension ameliorated the relationship between the at-risk CACNA1A genotype and XFG/XFGS; these findings should be confirmed in other studies.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.