OBJECTIVES: To determine whether candidate pharmacodynamic (beta-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 beta-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 1 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.
OBJECTIVES: To determine whether candidate pharmacodynamic (beta-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 beta-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 1 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.
Authors: Catherine A McCarty; Richard Berg; Richard Patchett; Russell A Wilke; James K Burmester Journal: Ophthalmic Genet Date: 2011-11-07 Impact factor: 1.803
Authors: Frank S Ong; Jane Z Kuo; Wei-Chi Wu; Ching-Yu Cheng; Wendell-Lamar B Blackwell; Brian L Taylor; Wayne W Grody; Jerome I Rotter; Chi-Chun Lai; Tien Y Wong Journal: J Pers Med Date: 2013