Pharmacogenetics of Ophthalmic Topical β-Blockers

Abstract

Glaucoma is the second leading cause of blindness worldwide. The primary glaucoma risk factor is elevated intraocular pressure. Topical β-blockers are affordable and widely used to lower intraocular pressure. Genetic variability has been postulated to contribute to interpersonal differences in efficacy and safety of topical β-blockers. This review summarizes clinically significant polymorphisms that have been identified in the β-adrenergic receptors (ADRB1, ADRB2 and ADRB3). The implications of polymorphisms in CYP2D6 are also discussed. Although the candidate-gene approach has facilitated significant progress in our understanding of the genetic basis of glaucoma treatment response, most drug responses involve a large number of genes, each containing multiple polymorphisms. Genome-wide association studies may yield a more comprehensive set of polymorphisms associated with glaucoma outcomes. An understanding of the genetic mechanisms associated with variability in individual responses to topical β-blockers may advance individualized treatment at a lower cost.

Keywords::

• β-adrenergic receptor
• β-blocker
• CYP2D6
• glaucoma
• IOP
• polymorphisms
• timolol

Financial & competing interests disclosure

This work was funded, in part, by start-up funds from the Department of Ophthalmology at the Medical College of Wisconsin (DJS), and Glaucoma Research, American Health Assistance Foundation (CAM). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

This work was funded, in part, by start-up funds from the Department of Ophthalmology at the Medical College of Wisconsin (DJS), and Glaucoma Research, American Health Assistance Foundation (CAM). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.