Intraocular pressure response to topical β-blockers associated with an ADRB2 single-nucleotide polymorphism

Objectives: To determine whether candidate pharmacodynamic (P-adrenergic receptor) and pharmacokinetic (cytochrome P450 2D6) gene polymorphisms are associated with the intraocular pressure (IOP) response to topical beta-blockers. Methods: Medical records of 18 773 adults in the Personalized Medicine Research Project were searched to extract all IOP measurements for subjects who had been prescribed a topical P-blocker. Five single-nucleotide polymorphisms in the beta(1)-, beta(2)-, and beta(3)-adrenergic receptor genes and 6 polymorphisms in the CYP2D6 gene were genotyped. Results: A total of 58.1% of the subjects were female; the mean age was 63.8 years. Topical beta-blockers were prescribed for 343 eyes of 215 subjects. An IOP reduction of 20% or more in I or both eyes was observed in 61.0% of subjects. Men were significantly more likely than women to have an IOP decrease of 20% or more (69.3% vs 54.9%, respectively; chi(2) = 4.48; P =.04). After adjusting for sex, family history of glaucoma, and use of systemic beta-blockers, subjects with the CC genotype at coding single-nucleotide polymorphism rs1042714 in the ADRB2 gene were significantly more likely to experience an IOP decrease of 20% or more (odds ratio, 2.00; 95% confidence interval, 1.00-4.02). Conclusion: We found that a coding single-nucleotide polymorphism in ADRB2 is associated with an increased likelihood of a clinically meaningful IOP response to topical beta-blockers. Clinical Relevance: Because topical beta-blockers are the least expensive class of agents used to lower IOP, genotype-based drug prescribing could save health care dollars.