Amlodipine increases risk of primary open-angle glaucoma.

Area of Science:

• Ophthalmology
• Pharmacology
• Genetics

Background:

• Calcium channel blockers are statistically linked to primary open-angle glaucoma (POAG).
• Previous studies indicated a 23% increased POAG risk in users of calcium channel blockers.
• The genetic underpinnings of this association remained unexamined.

Purpose of the Study:

• To confirm the association between amlodipine and POAG.
• To investigate the role of specific POAG-associated genes in this relationship.
• To evaluate amlodipine's effect on intraocular pressure (IOP).

Main Methods:

• Utilized MedWatch and UK Biobank data to assess amlodipine's impact on POAG and IOP.
• Analyzed three POAG-associated single-nucleotide polymorphisms (SNPs): rs9913911 (GAS7), rs944801 (CDKN2B-AS1), and rs2093210 (SIX6).
• Employed multivariate logistic regression for data analysis.

Main Results:

• Amlodipine use was associated with a significant increase in POAG prevalence (0.0805% to 0.177% in MedWatch data).
• UK Biobank analysis showed increased POAG risk with age, male sex, specific alleles of GAS7 and CDKN2B-AS1, and SIX6.
• Amlodipine use increased POAG risk by 16.1% (P=0.032) but was not linked to elevated IOP.
• CDKN2B-AS1 and SIX6, POAG genes not associated with IOP, showed association with POAG and amlodipine.

Conclusions:

• Amlodipine, a first-line antihypertensive, presents a potential risk for POAG development.
• This finding suggests alternative antihypertensives should be considered for patients with glaucoma or at risk.
• Diuretics and beta-blockers are viable alternatives as they are not associated with POAG or increased IOP.